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Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Microrna-605-3p Inhibited the Growth and Chemoresistance of Osteosarcoma Cells via Negatively Modulating RAF1

In Press, (this is not the final "Version of Record"). Available online 29 July, 2024
Author(s): Mao Wang, Weina Li, Guohui Han, Xiangdong Bai* and Jun Xie*
Published on: 29 July, 2024

DOI: 10.2174/0109298665314658240712051206

open access plus

Abstract

Background: Osteosarcoma (OS) is the leading cancer-associated mortality in childhood and adolescence. Increasing evidence has demonstrated the key function of microRNAs (miRNAs) in OS development and chemoresistance. Among them, miRNA-605-3p acted as an important tumor suppressor and was frequently down-regulated in multiple cancers. However, the function of miR-650-3p in OS has not been reported.

Objective: The aim of this work is to explore the novel role of miR-605-3p in osteosarcoma and its possible involvement in OS chemotherapy resistance.

Method: The expression levels of miR-605-3p in OS tissues and cells were assessed by reverse transcription quantitative PCR (RT-qPCR). The relevance of miR-605-3p with the prognosis of OS patients was determined by the Kaplan-Meier analysis. Additionally, the influence of miR-605-3p on OS cell growth was analyzed using the cell counting kit-8, colony formation assay, and flow cytometry. The mRNA and protein expression of RAF1 were detected by RT-qPCR and western blot. The binding of miR-605-3p with the 3’-UTR of RAF1 was confirmed by dual-luciferase reporter assay.

Results: Our results showed that miR-605-3p was markedly decreased in OS tissues and cells. A lower level of miR-605-3p was strongly correlated with lymph node metastasis and poor 5-year overall survival rate of OS patients. In vitro assay found that miR-605-3p suppressed OS cell proliferation and promoted cell apoptosis. Mechanistically, the proto-oncogene RAF1 was seen as a target of miR-605-3p and strongly suppressed by miR-605-3p in OS cells. Restoration of RAF1 markedly eliminated the inhibitory effect of miR-605-3p on OS progression, suggesting RAF1 as a key mediator of miR-605-3p. Consistent with the decreased level of RAF1, miR-605-3p suppressed the activation of both MEK and ERK in OS cells, which are the targets of RAF1. Moreover, lower levels of miR-605-3p were found in chemoresistant OS patients, and downregulated miR-605-3p increased the resistance of OS cells to therapeutic agents.

Conclusion: Our data revealed that miR-605-3p serves as a tumor suppressor gene by regulating RAF1 and increasing the chemosensitivity of OS cells, which provided the novel working mechanism of miR-605-3p in OS. Engineering stable nanovesicles that could efficiently deliver miR-605-3p with therapeutic activity into tumors could be a promising therapeutic approach for the treatment of OS.

[1]
Gazouli, I.; Kyriazoglou, A.; Kotsantis, I.; Anastasiou, M.; Pantazopoulos, A.; Prevezanou, M.; Chatzidakis, I.; Kavourakis, G.; Economopoulou, P.; Kontogeorgakos, V.; Papagelopoulos, P.; Psyrri, A. Systematic review of recurrent osteosarcoma systemic therapy. Cancers, 2021, 13(8), 1757.
[http://dx.doi.org/10.3390/cancers13081757] [PMID: 33917001]
[2]
Zhao, X.; Wu, Q.; Gong, X.; Liu, J.; Ma, Y. Osteosarcoma: A review of current and future therapeutic approaches. Biomed. Eng. Online, 2021, 20(1), 24.
[http://dx.doi.org/10.1186/s12938-021-00860-0] [PMID: 33653371]
[3]
Jiang, Z.Y.; Liu, J.B.; Wang, X.F.; Ma, Y.S.; Fu, D. Current status and prospects of clinical treatment of osteosarcoma. Technol. Cancer Res. Treat., 2022, 21, 15330338221124696.
[http://dx.doi.org/10.1177/15330338221124696] [PMID: 36128851]
[4]
Stefani, G.; Slack, F.J. Small non-coding RNAs in animal development. Nat. Rev. Mol. Cell Biol., 2008, 9(3), 219-230.
[http://dx.doi.org/10.1038/nrm2347] [PMID: 18270516]
[5]
Bartel, D.P. MicroRNAs. Cell, 2004, 116(2), 281-297.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[6]
Fabian, M.R.; Sonenberg, N.; Filipowicz, W. Regulation of mRNA translation and stability by microRNAs. Annu. Rev. Biochem., 2010, 79(1), 351-379.
[http://dx.doi.org/10.1146/annurev-biochem-060308-103103] [PMID: 20533884]
[7]
Fasoulakis, Z.; Daskalakis, G.; Diakosavvas, M.; Papapanagiotou, I.; Theodora, M.; Bourazan, A. MicroRNAs determining carcinogenesis by regulating oncogenes and tumor suppressor genes during cell cycle. MicroRNA, 2019, 9(2), 82-92.
[http://dx.doi.org/10.2174/2211536608666190919161849] [PMID: 31538910]
[8]
Farazi, T.A.; Spitzer, J.I.; Morozov, P.; Tuschl, T. miRNAs in human cancer. J. Pathol., 2011, 223(2), 102-115.
[http://dx.doi.org/10.1002/path.2806] [PMID: 21125669]
[9]
Asadzadeh, Z.; Mansoori, B.; Mohammadi, A.; Aghajani, M.; Haji-Asgarzadeh, K.; Safarzadeh, E. microRNAs in cancer stem cells: Biology, pathways, and therapeutic opportunities. J. Cell. Physiol., 2018, 234(7), 10002-10017.
[http://dx.doi.org/10.1002/jcp.27885] [PMID: 30537109]
[10]
Dong, Z.; Liao, Z.; He, Y.; Wu, C.; Meng, Z.; Qin, B.; Xu, G.; Li, Z.; Sun, T.; Wen, Y.; Li, G. Advances in the biological functions and mechanisms of miRNAs in the development of osteosarcoma. Technol. Cancer Res. Treat., 2022, 21, 15330338221117386.
[http://dx.doi.org/10.1177/15330338221117386] [PMID: 35950243]
[11]
Fan, L.; Zhong, Z.; Lin, Y.; Li, J. Non-coding RNAs as potential biomarkers in osteosarcoma. Front. Genet., 2022, 13, 1028477.
[http://dx.doi.org/10.3389/fgene.2022.1028477] [PMID: 36338952]
[12]
Liu, J.; Shang, G. The roles of noncoding rnas in the development of osteosarcoma stem cells and potential therapeutic targets. Front. Cell Dev. Biol., 2022, 10, 773038.
[http://dx.doi.org/10.3389/fcell.2022.773038] [PMID: 35252166]
[13]
Scuderi, S.A.; Calabrese, G.; Paterniti, I.; Campolo, M.; Lanza, M.; Capra, A.P.; Pantaleo, L.; Munaò, S.; Colarossi, L.; Forte, S.; Cuzzocrea, S.; Esposito, E. The biological function of MicroRNAs in bone tumors. Int. J. Mol. Sci., 2022, 23(4), 2348.
[http://dx.doi.org/10.3390/ijms23042348] [PMID: 35216464]
[14]
Soghli, N.; Ferns, G.A.; Sadeghsoltani, F.; Qujeq, D.; Yousefi, T.; Vaghari-Tabari, M. MicroRNAs and osteosarcoma: Potential targets for inhibiting metastasis and increasing chemosensitivity. Biochem. Pharmacol., 2022, 201, 115094.
[http://dx.doi.org/10.1016/j.bcp.2022.115094] [PMID: 35588853]
[15]
Pan, M.Z.; Song, Y.L.; Gao, F. MiR-605-3p inhibits malignant progression of prostate cancer by up-regulating EZH2. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(20), 8795-8805.
[http://dx.doi.org/10.26355/eurrev_201910_19274] [PMID: 31696466]
[16]
Hu, Y.L.; Feng, Y.; Chen, Y.Y.; Liu, J.Z.; Su, Y.; Li, P.; Huang, H.; Mao, Q.S.; Xue, W.J. SNHG16/miR‐605‐3p/TRAF6/NF‐κB feedback loop regulates hepatocellular carcinoma metastasis. J. Cell. Mol. Med., 2020, 24(13), 7637-7651.
[http://dx.doi.org/10.1111/jcmm.15399] [PMID: 32436333]
[17]
Pan, M.Z.; Song, Y.L.; Gao, F. MiR-605-3p inhibits malignant progression of prostate cancer by up-regulating EZH2. Eur. Rev. Med. Pharmacol. Sci., 2021, 25(5), 2156.
[http://dx.doi.org/10.26355/eurrev_202103_25197] [PMID: 33755945]
[18]
Su, Y.Z.; Cui, M.F.; Du, J.; Song, B. LncRNA DCST1-AS1 regulated cell proliferation, migration, invasion and apoptosis in gastric cancer by targeting miR-605-3p. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(3), 1158-1167.
[http://dx.doi.org/10.26355/eurrev_202002_20167] [PMID: 32096164]
[19]
Liu, N.; Hu, G.; Wang, H.; Wang, Y.; Guo, Z. LncRNA BLACAT1 regulates VASP expression via binding to miR‐605‐3p and promotes giloma development. J. Cell. Physiol., 2019, 234(12), 22144-22152.
[http://dx.doi.org/10.1002/jcp.28778] [PMID: 31093978]
[20]
Rosic, G. Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials. Adv. Biol. Earth Sci., 2024, 9(Special Issue), 11-34.
[http://dx.doi.org/10.62476/abes9s11]
[21]
Khalilov, R.K. Future prospects of biomaterials in nanomedicine. Adv. Biol. Earth Sci., 2024, 9, 5-10.
[http://dx.doi.org/10.62476/abes.9s5]
[22]
Huseynov, E. Novel nanomaterials for hepatobiliary diseases treatment and future perspectives. Adv. Biol. Earth Sci., 2024, 9, 81-91.
[http://dx.doi.org/10.62476/abes9s81]
[23]
Miwa, W.; Yasuda, J.; Yashima, K.; Makino, R.; Sekiya, T. Absence of activating mutations of the RAF1 protooncogene in human lung cancer. Biol. Chem. Hoppe Seyler, 1994, 375(10), 705-710.
[http://dx.doi.org/10.1515/bchm3.1994.375.10.705] [PMID: 7888083]
[24]
Borovski, T.; Vellinga, T.T.; Laoukili, J.; Santo, E.E.; Fatrai, S.; van Schelven, S.; Verheem, A.; Marvin, D.L.; Ubink, I.; Borel Rinkes, I.H.M.; Kranenburg, O. Inhibition of RAF1 kinase activity restores apicobasal polarity and impairs tumour growth in human colorectal cancer. Gut, 2017, 66(6), 1106-1115.
[http://dx.doi.org/10.1136/gutjnl-2016-311547] [PMID: 27670374]
[25]
Tian, H.; Yin, L.; Ding, K.; Xia, Y.Y.; Wang, X.H.; Wu, J.Z.; He, X. Raf1 is a prognostic factor for progression in patients with non small cell lung cancer after radiotherapy. Oncol. Rep., 2018, 39(4), 1966-1974.
[http://dx.doi.org/10.3892/or.2018.6277] [PMID: 29484414]
[26]
Zhang, L.; Pattanayak, A.; Li, W.; Ko, H.K.; Fowler, G.; Gordon, R. A multi-functional therapy approach for cancer: Targeting Raf1- mediated inhibition of cell motility, growth and interaction with the microenvironment. Mol. Cancer Ther., 2019, 19(1), 39-51.
[http://dx.doi.org/10.1158/1535-7163.MCT-19-0222] [PMID: 31582531]
[27]
Yang, G.; Wu, Y.; Wan, R.; Sang, H.; Liu, H.; Huang, W. The role of non coding RNAs in the regulation, diagnosis, prognosis and treatment of osteosarcoma (Review). Int. J. Oncol., 2021, 59(3), 69.
[http://dx.doi.org/10.3892/ijo.2021.5249] [PMID: 34296296]
[28]
Zeng, Z.; Zhou, W.; Duan, L.; Zhang, J.; Lu, X.; Jin, L.; Yu, Y. Circular RNA circ‐VANGL1 as a competing endogenous RNA contributes to bladder cancer progression by regulating miR‐605‐3p/VANGL1 pathway. J. Cell. Physiol., 2019, 234(4), 3887-3896.
[http://dx.doi.org/10.1002/jcp.27162] [PMID: 30146736]
[29]
Chen, L.; Wang, Q.; Wang, G.; Wang, H.; Huang, Y.; Liu, X.; Cai, X. miR‐16 inhibits cell proliferation by targeting IGF1R and the Raf1–MEK1/2–ERK1/2 pathway in osteosarcoma. FEBS Lett., 2013, 587(9), 1366-1372.
[http://dx.doi.org/10.1016/j.febslet.2013.03.007] [PMID: 23507142]
[30]
Chai, J.; Wang, S.; Han, D.; Dong, W.; Xie, C.; Guo, H. MicroRNA-455 inhibits proliferation and invasion of colorectal cancer by targeting RAF proto-oncogene serine/threonine-protein kinase. Tumour Biol., 2015, 36(2), 1313-1321.
[http://dx.doi.org/10.1007/s13277-014-2766-3] [PMID: 25355599]
[31]
Wang, T.H.; Hsueh, C.; Chen, C.C.; Li, W.S.; Yeh, C.T.; Lian, J.H.; Chang, J.L.; Chen, C.Y. Melatonin inhibits the progression of hepatocellular carcinoma through MicroRNA Let7i-3p mediated RAF1 reduction. Int. J. Mol. Sci., 2018, 19(9), 2687.
[http://dx.doi.org/10.3390/ijms19092687] [PMID: 30201903]
[32]
Wang, F. Jiang, ; Sun, Q.; Yan, ; Wang, ; Fu, ; Liu, ; Hu, miR-195 is a key regulator of Raf1 in thyroid cancer. OncoTargets Ther., 2015, 8, 3021-3028.
[http://dx.doi.org/10.2147/OTT.S90710] [PMID: 26527888]
[33]
Tao, L.; Zhang, C.Y.; Guo, L.; Li, X.; Han, N.N.; Zhou, Q.; Liu, Z.L. Retracted: MicroRNA‐497 accelerates apoptosis while inhibiting proliferation, migration, and invasion through negative regulation of the MAPK/ERK signaling pathway via RAF‐1. J. Cell. Physiol., 2018, 233(10), 6578-6588.
[http://dx.doi.org/10.1002/jcp.26272] [PMID: 29150931]

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      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=51) and sj.journal_id!=51 group by `j`.`nid`) as `aggregate_table`
      1.08msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=51) and sj.journal_id!=51 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.05msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=51) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      7.07msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=51) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      13.29msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '141990'
      320μsalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 141990
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '141990'
      6.82msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 141990
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '141990' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.23msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 141990
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      370μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      660μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 51 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      43.12msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 51 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      18.39msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 51 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      17.03msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 141990 limit 1
      300μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 141990
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 141990 and content_type = 'article' order by status desc limit 1
      370μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 232407 limit 1
      270μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 232407
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      310μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'PPL' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      340μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: PPL
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '141990' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      560μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      260μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      320μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 141990 limit 1
      3.96msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 141990
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 51 and `b`.`banner_from_date` <= 1740474162 and `b`.`banner_to_date` >= 1740474162 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.77msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 51
      • 3: 1740474162
      • 4: 1740474162
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 51 and `b`.`banner_from_date` <= 1740474162 and `b`.`banner_to_date` >= 1740474162 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.73msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 51
      • 3: 1740474162
      • 4: 1740474162
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='928fa21e7ba04435b45595b903d4946d'
      300μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        NYLlfJHb6FzFtEiB5y5j6P5kyjymsGeP48SbJ0aa
        uc_cart_id
        928fa21e7ba04435b45595b903d4946d
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/article/141990" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/141990
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
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