Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

LINC00461 Knockdown Enhances the Effect of Ixazomib in Multiple Myeloma Cells

Author(s): Mingyang Deng, Huan Yuan, Hongling Peng, Sufang Liu, Xiang Xiao, Zhihua Wang, Guangsen Zhang and Han Xiao*

Volume 23, Issue 8, 2023

Published on: 27 April, 2023

Page: [643 - 652] Pages: 10

DOI: 10.2174/1568009623666230316152713

Price: $65

Abstract

Background: LINC00461 has been implicated to be involved in several types of cancer while its roles in multiple myeloma remain unclear. Our study aims to investigate the roles of LINC00461 in multiple myeloma and explore its effects on ixazomib therapy.

Methods: LINC00461 and small nuclear ribonucleoprotein polypeptide (SNRP) B2 knockdown stable cell lines were constructed. Cell viability assays including MTT, cell number counting, and colony formation were performed. RNA-pull down and immunoblotting assays were conducted to determine the intramolecular interactions. qRT-PCR and western blotting were conducted to determine the levels of target genes. Kaplan-Meier analysis was used to evaluate overall survival rates.

Results: Knockdown of LINC00461 or SNRPB2 enhanced ixazomib's cytotoxicity, as well as affected its regulatory effects on cell apoptosis and cell cycle distribution. Further results showed that LINC00461 knockdown reduced the expression levels of SNRPB2 by their interactions. Additionally, a positive correlation between LINC00461 and SNRPB2 was found in patients with multiple myeloma. Low expression of SNRPB2 was associated with a high survival rate in patients with multiple myeloma.

Conclusion: Knockdown of LINC00461 enhanced the therapeutic effects of ixazomib against multiple myeloma in part by the regulation of SNRPB2.

« Previous Next »
Graphical Abstract

[1]
Wood, A.J.J.; Alexanian, R.; Dimopoulos, M. The treatment of multiple myeloma. N. Engl. J. Med., 1994, 330(7), 484-489.
[http://dx.doi.org/10.1056/NEJM199402173300709] [PMID: 8289856]
[2]
Bird, S. A.; Boyd, K. Multiple myeloma: An overview of management. Palliative care and social practice, 2019, 13, 1178224219868235.
[http://dx.doi.org/10.1177/1178224219868235] [PMID: 32215370]
[3]
Becker, N. Epidemiology of multiple myeloma. Recent Results Cancer Res., 2011, 183, 25-35.
[http://dx.doi.org/10.1007/978-3-540-85772-3_2] [PMID: 21509679]
[4]
Rajkumar, S.V. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am. J. Hematol., 2016, 91(7), 719-734.
[http://dx.doi.org/10.1002/ajh.24402] [PMID: 27291302]
[5]
Ludwig, H.; Novis Durie, S.; Meckl, A.; Hinke, A.; Durie, B. Multiple myeloma incidence and mortality around the Globe; interrelations between health access and quality, economic resources, and patient empowerment. Oncologist, 2020, 25(9), e1406-e1413.
[http://dx.doi.org/10.1634/theoncologist.2020-0141] [PMID: 32335971]
[6]
Sharma, G.N.; Dave, R.; Sanadya, J.; Sharma, P.; Sharma, K.K. Various types and management of breast cancer: An overview. J. Adv. Pharm. Technol. Res., 2010, 1(2), 109-126.
[PMID: 22247839]
[7]
Greipp, P.R.; Miguel, J.S.; Durie, B.G.M.; Crowley, J.J.; Barlogie, B.; Bladé, J.; Boccadoro, M.; Child, J.A.; Avet-Loiseau, H.; Kyle, R.A.; Lahuerta, J.J.; Ludwig, H.; Morgan, G.; Powles, R.; Shimizu, K.; Shustik, C.; Sonneveld, P.; Tosi, P.; Turesson, I.; Westin, J. International staging system for multiple myeloma. J. Clin. Oncol., 2005, 23(15), 3412-3420.
[http://dx.doi.org/10.1200/JCO.2005.04.242] [PMID: 15809451]
[8]
Barlogie, B.; Shaughnessy, J.; Tricot, G.; Jacobson, J.; Zangari, M.; Anaissie, E.; Walker, R.; Crowley, J. Treatment of multiple myeloma. Blood, 2004, 103(1), 20-32.
[http://dx.doi.org/10.1182/blood-2003-04-1045] [PMID: 12969978]
[9]
Anderson, K. C. Lenalidomide and thalidomide: mechanisms of action-similarities and differences. Semin. Hematol., 2005, 42(4 Suppl 4), S3-8.
[http://dx.doi.org/10.1053/j.seminhematol.2005.10.001] [PMID: 16344099]
[10]
Mahindra, A.; Laubach, J.; Raje, N.; Munshi, N.; Richardson, P.G.; Anderson, K. Latest advances and current challenges in the treatment of multiple myeloma. Nat. Rev. Clin. Oncol., 2012, 9(3), 135-143.
[http://dx.doi.org/10.1038/nrclinonc.2012.15] [PMID: 22349016]
[11]
Naymagon, L.; Abdul-Hay, M. Novel agents in the treatment of multiple myeloma: A review about the future. J. Hematol. Oncol., 2016, 9(1), 52.
[http://dx.doi.org/10.1186/s13045-016-0282-1] [PMID: 27363832]
[12]
Muz, B.; Ghazarian, R.N.; Ou, M.; Luderer, M.J.; Kusdono, H.D.; Azab, A.K. Spotlight on ixazomib: Potential in the treatment of multiple myeloma. Drug Des. Devel. Ther., 2016, 10, 217-226.
[PMID: 26811670]
[13]
Spizzo, R.; Almeida, M.I.; Colombatti, A.; Calin, G.A. Long non-coding RNAs and cancer: A new frontier of translational research? Oncogene, 2012, 31(43), 4577-4587.
[http://dx.doi.org/10.1038/onc.2011.621] [PMID: 22266873]
[14]
Arun, G.; Diermeier, S.D.; Spector, D.L. Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol. Med., 2018, 24(3), 257-277.
[http://dx.doi.org/10.1016/j.molmed.2018.01.001] [PMID: 29449148]
[15]
Do, H.; Kim, W. Roles of oncogenic long non-coding RNAs in cancer development. Genomics Inform., 2018, 16(4), e18.
[http://dx.doi.org/10.5808/GI.2018.16.4.e18] [PMID: 30602079]
[16]
Majidinia, M.; Yousefi, B. Long non-coding RNAs in cancer drug resistance development. DNA Repair (Amst.), 2016, 45, 25-33.
[http://dx.doi.org/10.1016/j.dnarep.2016.06.003] [PMID: 27427176]
[17]
Yang, Y.; Ren, M.; Song, C.; Li, D.; Soomro, S.H.; Xiong, Y.; Zhang, H.; Fu, H. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget, 2017, 8(48), 84123-84139.
[http://dx.doi.org/10.18632/oncotarget.20340] [PMID: 29137410]
[18]
Ji, D.; Wang, Y.; Li, H.; Sun, B.; Luo, X. Long non-coding RNA LINC00461/miR-149-5p/LRIG2 axis regulates hepatocellular carcinoma progression. Biochem. Biophys. Res. Commun., 2019, 512(2), 176-181.
[http://dx.doi.org/10.1016/j.bbrc.2019.03.049] [PMID: 30879766]
[19]
Yu, H.; Ma, J.; Chen, J.; Yang, Y.; Liang, J.; Liang, Y. LncRNA LINC00461 promotes colorectal cancer progression via miRNA-323b-3p/NFIB Axis. OncoTargets Ther., 2019, 12, 11119-11129.
[http://dx.doi.org/10.2147/OTT.S228798]
[20]
Hou, J.; Wang, Y.; Zhang, H.; Hu, Y.; Xin, X.; Li, X. Silencing of LINC00461 enhances radiosensitivity of lung adenocarcinoma cells by down‐regulating HOXA10 via microRNA‐195. J. Cell. Mol. Med., 2020, 24(5), 2879-2890.
[http://dx.doi.org/10.1111/jcmm.14859] [PMID: 31967713]
[21]
Dong, L.; Qian, J.; Chen, F.; Fan, Y.; Long, J. LINC00461 promotes cell migration and invasion in breast cancer through miR‐30a‐5p/integrin β3 axis. J. Cell. Biochem., 2019, 120(4), 4851-4862.
[http://dx.doi.org/10.1002/jcb.27435] [PMID: 30623482]
[22]
Yang, Y.; Lei, H.; Qiang, Y.; Wang, B. Ixazomib enhances parathyroid hormone–induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor. Mol. Biol. Cell, 2017, 28(13), 1792-1803.
[http://dx.doi.org/10.1091/mbc.e17-02-0096] [PMID: 28495797]
[23]
Clemens, J.; Welti, L.; Schäfer, J.; Seckinger, A.; Burhenne, J.; Theile, D.; Weiss, J. Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter-based drug-drug interactions. Oncol. Lett., 2017, 14(3), 3185-3192.
[http://dx.doi.org/10.3892/ol.2017.6560] [PMID: 28927064]
[24]
Wang, Q.; Dong, Z.; Su, J.; Huang, J.; Xiao, P.; Tian, L.; Chen, Y.; Ma, L.; Chen, X. Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochem. Biophys. Res. Commun., 2021, 549, 1-7.
[http://dx.doi.org/10.1016/j.bbrc.2021.02.048] [PMID: 33647537]
[25]
Naudin, C.; Hattabi, A.; Michelet, F.; Miri-Nezhad, A.; Benyoucef, A.; Pflumio, F.; Guillonneau, F.; Fichelson, S.; Vigon, I.; Dusanter-Fourt, I.; Lauret, E. PUMILIO/FOXP1 signaling drives expansion of hematopoietic stem/progenitor and leukemia cells. Blood, 2017, 129(18), 2493-2506.
[http://dx.doi.org/10.1182/blood-2016-10-747436] [PMID: 28232582]
[26]
Liu, C.; Shen, Y.J.; Tu, Q.B.; Zhao, Y.R.; Guo, H.; Wang, J.; Zhang, L.; Shi, H.W.; Sun, Y. Pedunculoside, a novel triterpene saponin extracted from Ilex rotunda, ameliorates high-fat diet induced hyperlipidemia in rats. Biomed. Pharmacother., 2018, 101, 608-616.
[http://dx.doi.org/10.1016/j.biopha.2018.02.131] [PMID: 29518607]
[27]
Guo, H.; Qi, R.Q.; Sheng, J.; Liu, C.; Ma, H.; Wang, H.X.; Li, J.H.; Gao, X.H.; Wan, Y.S.; Chen, H.D. MiR-155, a potential serum marker of extramammary Paget’s disease. BMC Cancer, 2018, 18(1), 1078.
[http://dx.doi.org/10.1186/s12885-018-4994-1] [PMID: 30458743]
[28]
Deng, M.; Yuan, H.; Liu, S.; Hu, Z.; Xiao, H. Exosome-transmitted LINC00461 promotes multiple myeloma cell proliferation and suppresses apoptosis by modulating microRNA/BCL-2 expression. Cytotherapy, 2019, 21(1), 96-106.
[http://dx.doi.org/10.1016/j.jcyt.2018.10.006] [PMID: 30409700]
[29]
Deng, M.; Yuan, H.; Peng, H.; Liu, S.; Xiao, X.; Wang, Z.; Zhang, G.; Xiao, H. Mesenchymal stem cells inhibit the effects of dexamethasone in multiple myeloma cells. Stem Cells Int., 2022, 2022, 4855517.
[http://dx.doi.org/10.1155/2022/4855517] [PMID: 35419059]
[30]
Wu, Y.; Zhang, Z.; Wu, J.; Hou, J.; Ding, G. The exosomes containing LINC00461 originated from multiple myeloma inhibit the osteoblast differentiation of bone mesenchymal stem cells via sponging miR-324-3p. J. Healthcare Eng., 2022, 2022, 3282860.
[http://dx.doi.org/10.1155/2022/3282860] [PMID: 35126917]
[31]
Tsai, M.C.; Spitale, R.C.; Chang, H.Y. Long intergenic noncoding RNAs: New links in cancer progression. Cancer Res., 2011, 71(1), 3-7.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2483] [PMID: 21199792]
[32]
Huarte, M. The emerging role of lncRNAs in cancer. Nat. Med., 2015, 21(11), 1253-1261.
[http://dx.doi.org/10.1038/nm.3981] [PMID: 26540387]
[33]
Kyle, R. A. Targeted therapy of multiple myeloma. Hematology, 2012, 17(Suppl. 1), s125-s128.
[http://dx.doi.org/10.1179/102453312X13336169156339]
[34]
Moreau, P.; Richardson, P.G.; Cavo, M.; Orlowski, R.Z.; San Miguel, J.F.; Palumbo, A.; Harousseau, J.L. Proteasome inhibitors in multiple myeloma: 10 years later. Blood, 2012, 120(5), 947-959.
[http://dx.doi.org/10.1182/blood-2012-04-403733] [PMID: 22645181]
[35]
Brayer, J.; Baz, R. The potential of ixazomib, a second-generation proteasome inhibitor, in the treatment of multiple myeloma. Ther. Adv. Hematol., 2017, 8(7), 209-220.
[http://dx.doi.org/10.1177/2040620717710171] [PMID: 28694935]
[36]
Turunen, J.J.; Niemelä, E.H.; Verma, B.; Frilander, M.J. The significant other: Splicing by the minor spliceosome. Wiley Interdiscip. Rev. RNA, 2013, 4(1), 61-76.
[http://dx.doi.org/10.1002/wrna.1141] [PMID: 23074130]
[37]
Luo, Y.; Lin, J.; Zhang, Y.; Dai, G.; Li, A.; Liu, X. LncRNA PCAT6 predicts poor prognosis in hepatocellular carcinoma and promotes proliferation through the regulation of cell cycle arrest and apoptosis. Cell Biochem. Funct., 2020, 38(7), 895-904.
[http://dx.doi.org/10.1002/cbf.3510] [PMID: 32064636]
[38]
Huang, H.H.; Ferguson, I.D.; Thornton, A.M.; Bastola, P.; Lam, C.; Lin, Y.H.T.; Choudhry, P.; Mariano, M.C.; Marcoulis, M.D.; Teo, C.F.; Malato, J.; Phojanakong, P.J.; Martin, T.G., III; Wolf, J.L.; Wong, S.W.; Shah, N.; Hann, B.; Brooks, A.N.; Wiita, A.P. Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma. Nat. Commun., 2020, 11(1), 1931.
[http://dx.doi.org/10.1038/s41467-020-15521-4] [PMID: 32321912]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy