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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

miR-4295 Promotes the Malignant Progression of Gastric Cancer via Targeting PTEN

Author(s): Xiaoyan Yang, Jing Yang, Yunlian Tang, Zhizhong Xie, Yang Zhang, Xiaoyong Lei* and Runliang Gan*

Volume 25, Issue 11, 2022

Published on: 14 January, 2022

Page: [1897 - 1906] Pages: 10

DOI: 10.2174/1386207325666211110095307

Price: $65

Abstract

Background: Gastric cancer (GC), one of the common clinical malignant tumors of the digestive system, is the fourth most commonly diagnosed cancer and the second lethal cancer worldwide and has the characteristics of high metastasis, fatality, and recurrence rate. This research was conducted to investigate the role and mechanism of miR-4295 in gastric cancer.

Methods: The expression capacity of miR-4295 was determined in gastric cancer tissues and its normal tissues by qRT-PCR. PTEN expression level was detected by western blot. SGC-7901 and MGC-803 cell lines were cultured and transfected with miR-4295 or its inhibitor. The effects of miR-4295 on cell proliferation, colony formation, migration, and invasion in vitro were investigated. The mutual effect between miR-4295 and PTEN in 293T cells was explored by luciferase reporter gene assays.

Results: The results showed that miR-4295 expression was higher in gastric cancer tissues and cell lines, and the miR-4295 level was significantly negatively associated with the tumor size and distal metastasis of gastric cancer. Notably, up-regulated miR-4295 promoted cell proliferation, migration and invasion in vitro, whereas it led to contrary effects while down-regulating miR-4295 expression. Further mechanism studies displayed that miR-4295 could directly fasten the PTEN 3’UTR and dramatically decrease the level of PTEN in vitro.

Conclusion: The findings revealed that miR-4295 could promote gastric cancer cell proliferation, migration and invasion, which might be attributed to targeting PTEN. Our study suggested that miR-4295 might be a potential therapeutic target for gastric cancer.

Keywords: miR-4295, proliferation, migration, invasion, PTEN, gastric cancer.

Graphical Abstract

[1]
Shmulevich, I. Large-scale molecular characterization and analysis of gastric cancer. Chin. J. Cancer, 2014, 33(8), 369-370.
[PMID: 25313412]
[2]
Hamashima, C. Current issues and future perspectives of gastric cancer screening. World J. Gastroenterol., 2014, 20(38), 13767-13774.
[http://dx.doi.org/10.3748/wjg.v20.i38.13767] [PMID: 25320514]
[3]
Wang, L.; Li, B.; Zhang, L.; Li, Q.; He, Z.; Zhang, X.; Huang, X.; Xu, Z.; Xia, Y.; Zhang, Q.; Li, Q.; Xu, J.; Sun, G.; Xu, Z. miR-664a-3p functions as an oncogene by targeting Hippo pathway in the development of gastric cancer. Cell Prolif., 2019, 52(3), e12567.
[http://dx.doi.org/10.1111/cpr.12567] [PMID: 30883979]
[4]
Ueda, T.; Volinia, S.; Okumura, H.; Shimizu, M.; Taccioli, C.; Rossi, S.; Alder, H.; Liu, C.G.; Oue, N.; Yasui, W.; Yoshida, K.; Sasaki, H.; Nomura, S.; Seto, Y.; Kaminishi, M.; Calin, G.A.; Croce, C.M. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol., 2010, 11(2), 136-146.
[http://dx.doi.org/10.1016/S1470-2045(09)70343-2] [PMID: 20022810]
[5]
Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer statistics, 2010. CA Cancer J. Clin., 2010, 60(5), 277-300.
[http://dx.doi.org/10.3322/caac.20073] [PMID: 20610543]
[6]
Cunningham, D.; Allum, W.H.; Stenning, S.P.; Thompson, J.N.; Van de Velde, C.J.; Nicolson, M.; Scarffe, J.H.; Lofts, F.J.; Falk, S.J.; Ive-son, T.J.; Smith, D.B.; Langley, R.E.; Verma, M.; Weeden, S.; Chua, Y.J. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N. Engl. J. Med., 2006, 355(1), 11-20.
[http://dx.doi.org/10.1056/NEJMoa055531] [PMID: 16822992]
[7]
Cheetham, S.W.; Gruhl, F.; Mattick, J.S.; Dinger, M.E. Long noncoding RNAs and the genetics of cancer. Br. J. Cancer, 2013, 108(12), 2419-2425.
[http://dx.doi.org/10.1038/bjc.2013.233] [PMID: 23660942]
[8]
Maruyama, R.; Suzuki, H.; Yamamoto, E.; Imai, K.; Shinomura, Y. Emerging links between epigenetic alterations and dysregulation of noncoding RNAs in cancer. Tumour Biol., 2012, 33(2), 277-285.
[http://dx.doi.org/10.1007/s13277-011-0308-9] [PMID: 22219034]
[9]
Zhou, Z.; Lin, Z.; Pang, X.; Tariq, M.A.; Ao, X.; Li, P.; Wang, J. Epigenetic regulation of long non-coding RNAs in gastric cancer. Oncotarget, 2017, 9(27), 19443-19458.
[http://dx.doi.org/10.18632/oncotarget.23821] [PMID: 29721215]
[10]
Song, S.; Ajani, J.A. The role of microRNAs in cancers of the upper gastrointestinal tract. Nat. Rev. Gastroenterol. Hepatol., 2013, 10(2), 109-118.
[http://dx.doi.org/10.1038/nrgastro.2012.210] [PMID: 23165235]
[11]
Correia de Sousa, M.; Gjorgjieva, M.; Dolicka, D.; Sobolewski, C.; Foti, M. Deciphering miRNAs’ action through miRNA Editing. Int. J. Mol. Sci., 2019, 20(24), 6249.
[http://dx.doi.org/10.3390/ijms20246249] [PMID: 31835747]
[12]
Bernardo, B.C.; Ooi, J.Y.; Lin, R.C.; McMullen, J.R. miRNA therapeutics: a new class of drugs with potential therapeutic applications in the heart. Future Med. Chem., 2015, 7(13), 1771-1792.
[http://dx.doi.org/10.4155/fmc.15.107] [PMID: 26399457]
[13]
Lin, S.; Gregory, R.I. MicroRNA biogenesis pathways in cancer. Nat. Rev. Cancer, 2015, 15(6), 321-333.
[http://dx.doi.org/10.1038/nrc3932] [PMID: 25998712]
[14]
Hu, S.; Zheng, Q.; Wu, H.; Wang, C.; Liu, T.; Zhou, W. miR-532 promoted gastric cancer migration and invasion by targeting NKD1. Life Sci., 2017, 177, 15-19.
[http://dx.doi.org/10.1016/j.lfs.2017.03.019] [PMID: 28356225]
[15]
Demiryas, S.; Kocazeybek, B.; Demirci, M.; Caliskan, R.; Kepil, N.; Uysal, H.K.; Dinc, H.O.; Saribas, S.; Ergin, S.; Erzin, Y.; Tasci, İ.; Erdamar, S.; Demirdag, C.; Tokman, H.B. Helicobacter pylori-miRNA interaction in gastric cancer tissues: First prospective study from Turkey. New Microbiol., 2019, 42(4), 210-220.
[PMID: 31524946]
[16]
Yang, Y.J.; Luo, S.; Wang, L.S. Effects of microRNA-378 on epithelial-mesenchymal transition, migration, invasion and prognosis in gastric carcinoma by targeting BMP2. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(12), 5176-5186.
[PMID: 31298369]
[17]
Liu, L.; Tian, Y.C.; Mao, G.; Zhang, Y.G.; Han, L. MiR-675 is frequently overexpressed in gastric cancer and enhances cell proliferation and invasion via targeting a potent anti-tumor gene PITX1. Cell. Signal., 2019, 62, 109352.
[http://dx.doi.org/10.1016/j.cellsig.2019.109352] [PMID: 31260797]
[18]
Meng, H.; Li, Y.Y.; Han, D.; Zhang, C.Y. MiRNA-93-5p promotes the biological progression of gastric cancer cells via Hippo signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(11), 4763-4769.
[PMID: 31210305]
[19]
Wei, W.; Cao, W.; Zhan, Z.; Yan, L.; Xie, Y.; Xiao, Q. MiR-1284 suppresses gastric cancer progression by targeting EIF4A1. OncoTargets Ther., 2019, 12, 3965-3976.
[http://dx.doi.org/10.2147/OTT.S191015] [PMID: 31190893]
[20]
Jin, M.; Zhang, G.W.; Shan, C.L.; Zhang, H.; Wang, Z.G.; Liu, S.Q.; Wang, S.Q. Up-regulation of miRNA-105 inhibits the progression of gastric carcinoma by directly targeting SOX9. Eur. Rev. Med. Pharmacol. Sci., 2019, 23(9), 3779-3789.
[PMID: 31115004]
[21]
Li, X.; Zheng, J.; Diao, H.; Liu, Y. RUNX3 is down-regulated in glioma by Myc-regulated miR-4295. J. Cell. Mol. Med., 2016, 20(3), 518-525.
[http://dx.doi.org/10.1111/jcmm.12736] [PMID: 26756701]
[22]
Nan, Y.H.; Wang, J.; Wang, Y.; Sun, P.H.; Han, Y.P.; Fan, L.; Wang, K.C.; Shen, F.J.; Wang, W.H. MiR-4295 promotes cell growth in blad-der cancer by targeting BTG1. Am. J. Transl. Res., 2016, 8(11), 4892-4901.
[PMID: 27904689]
[23]
Gao, Q.; Zheng, J. Ginsenoside Rh2 inhibits prostate cancer cell growth through suppression of microRNA-4295 that activates CDKN1A. Cell Prolif., 2018, 51(3), e12438.
[http://dx.doi.org/10.1111/cpr.12438] [PMID: 29457293]
[24]
Yan, R.; Li, K.; Yuan, D.W.; Wang, H.N.; Zhang, Y.; Dang, C.X.; Zhu, K. Downregulation of microRNA-4295 enhances cisplatin-induced gastric cancer cell apoptosis through the EGFR/PI3K/Akt signaling pathway by targeting LRIG1. Int. J. Oncol., 2018, 53(6), 2566-2578.
[http://dx.doi.org/10.3892/ijo.2018.4595] [PMID: 30320337]
[25]
Li, J.; Yen, C.; Liaw, D.; Podsypanina, K.; Bose, S.; Wang, S.I.; Puc, J.; Miliaresis, C.; Rodgers, L.; McCombie, R.; Bigner, S.H.; Giovanel-la, B.C.; Ittmann, M.; Tycko, B.; Hibshoosh, H.; Wigler, M.H.; Parsons, R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 1997, 275(5308), 1943-1947.
[http://dx.doi.org/10.1126/science.275.5308.1943] [PMID: 9072974]
[26]
Steck, P.A.; Pershouse, M.A.; Jasser, S.A.; Yung, W.K.; Lin, H.; Ligon, A.H.; Langford, L.A.; Baumgard, M.L.; Hattier, T.; Davis, T.; Frye, C.; Hu, R.; Swedlund, B.; Teng, D.H.; Tavtigian, S.V. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat. Genet., 1997, 15(4), 356-362.
[http://dx.doi.org/10.1038/ng0497-356] [PMID: 9090379]
[27]
Lee, Y.R.; Chen, M.; Pandolfi, P.P. The functions and regulation of the PTEN tumour suppressor: new modes and prospects. Nat. Rev. Mol. Cell Biol., 2018, 19(9), 547-562.
[http://dx.doi.org/10.1038/s41580-018-0015-0] [PMID: 29858604]
[28]
Zhao, D.; Lu, X.; Wang, G.; Lan, Z.; Liao, W.; Li, J.; Liang, X.; Chen, J.R.; Shah, S.; Shang, X.; Tang, M.; Deng, P.; Dey, P.; Chakravarti, D.; Chen, P.; Spring, D.J.; Navone, N.M.; Troncoso, P.; Zhang, J.; Wang, Y.A.; DePinho, R.A. Synthetic essentiality of chromatin remodel-ling factor CHD1 in PTEN-deficient cancer. Nature, 2017, 542(7642), 484-488.
[http://dx.doi.org/10.1038/nature21357] [PMID: 28166537]
[29]
Labbé, D.P.; Uetani, N.; Vinette, V.; Lessard, L.; Aubry, I.; Migon, E.; Sirois, J.; Haigh, J.J.; Bégin, L.R.; Trotman, L.C.; Paquet, M.; Trem-blay, M.L. PTP1B deficiency enables the ability of a high-fat diet to drive the invasive character of PTEN-deficient prostate cancers. Cancer Res., 2016, 76(11), 3130-3135.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1501] [PMID: 27020859]
[30]
Sheng, L.; He, P.; Yang, X.; Zhou, M.; Feng, Q. miR-612 negatively regulates colorectal cancer growth and metastasis by targeting AKT2. Cell Death Dis., 2015, 6(7), e1808.
[http://dx.doi.org/10.1038/cddis.2015.184] [PMID: 26158514]
[31]
Zhang, J.G.; Wang, J.J.; Zhao, F.; Liu, Q.; Jiang, K.; Yang, G.H. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in Non-Small Cell Lung Cancer (NSCLC). Clin. Chim. Acta, 2010, 411(11-12), 846-852.
[http://dx.doi.org/10.1016/j.cca.2010.02.074] [PMID: 20223231]
[32]
Lou, Y.; Yang, X.; Wang, F.; Cui, Z.; Huang, Y. MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int. J. Mol. Med., 2010, 26(6), 819-827.
[http://dx.doi.org/10.3892/ijmm_00000530] [PMID: 21042775]
[33]
Li, H.; Yu, B.; Li, J.; Su, L.; Yan, M.; Zhang, J.; Li, C.; Zhu, Z.; Liu, B. Characterization of differentially expressed genes involved in pathways associated with gastric cancer. PLoS One, 2015, 10(4), e0125013.
[http://dx.doi.org/10.1371/journal.pone.0125013] [PMID: 25928635]
[34]
McNamara, C.R.; Degterev, A. Small-molecule inhibitors of the PI3K signaling network. Future Med. Chem., 2011, 3(5), 549-565.
[http://dx.doi.org/10.4155/fmc.11.12] [PMID: 21526896]
[35]
Zhang, B.G.; Li, J.F.; Yu, B.Q.; Zhu, Z.G.; Liu, B.Y.; Yan, M. microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN. Oncol. Rep., 2012, 27(4), 1019-1026.
[http://dx.doi.org/10.3892/or.2012.1645] [PMID: 22267008]

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