Abstract
To verify the hypothesis that upregulation of microRNA-31 (miR-31) targeting integrin α5 (ITGA5) suppresses tumor cell invasion and metastasis by indirectly regulating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in human SGC7901 gastric cancer (GC) cells. The miRTarBase was used to predict whether ITGA5 is the target gene of miR-31, which was further confirmed by luciferase reporter gene assay. The SGC7901 GC cells were divided into five groups including the blank, miR-31 mimic, miR-31 mimic control, miR-31 inhibitor, and miR-31 inhibitor control groups. Reverse transcriptase-polymerase chain reaction (RT-PCR), western blotting, cell scratch test, and transwell assays were respectively performed in our study. TGA5 was found as the target gene of miR-31. The RT-PCR detection revealed that, compared with the blank group, ITGA5 messenger RNA (mRNA) expression decreased in the miR-31 mimic group, but increased in the miR-31 inhibitor group. The western blotting examination suggested that the expressions of ITGA5, PI3K, and AKT proteins reduced in the miR-31 mimic group, but enhanced in the miR-31 inhibitor group when compared to the blank group, respectively. The cell scratch and transwell assays indicated that the miR-31 expressions were negatively associated with GC cell migration and invasion. Besides, RT-PCR combined with western blotting demonstrated that the miR-31 expressions were higher in the normal tissues than those in the GC tissues, while the ITGA5 mRNA and protein showed lower expression in the normal tissues than they did in the GC tissues. Our study concluded that upregulation of miR-31 targeting ITGA5 may suppress tumor cell invasion and metastasis by indirectly regulating PI3K/AKT signaling pathway in human SGC7901 GC cells.
Similar content being viewed by others
Change history
21 December 2021
This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010"
References
Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575–81.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
Hu J, La Vecchia C, Negri E, de Groh M, Morrison H, Mery L, et al. Macronutrient intake and stomach cancer. Cancer Causes Control. 2015;26(6):839–47.
Montagnani F, Turrisi G, Marinozzi C, Aliberti C, Fiorentini G. Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2011;14(1):50–5.
Kim JG. Molecular targeted therapy for advanced gastric cancer. Korean J Intern Med. 2013;28(2):149–55.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (toga): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.
Zhao X, Dou W, He L, Liang S, Tie J, Liu C, et al. MicroRNA-7 functions as an anti-metastatic microRNA in gastric cancer by targeting insulin-like growth factor-1 receptor. Oncogene. 2013;32(11):1363–72.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215–33.
Laurila EM, Kallioniemi A. The diverse role of mir-31 in regulating cancer associated phenotypes. Genes Chromosomes Cancer. 2013;52(12):1103–13.
Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA. Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of mir-31 on metastasis. Cancer Res. 2010;70(12):5147–54.
Johnson MS, Lu N, Denessiouk K, Heino J, Gullberg D. Integrins during evolution: evolutionary trees and model organisms. Biochim Biophys Acta. 2009;1788(4):779–89.
Augoff K, Das M, Bialkowska K, McCue B, Plow EF, Sossey-Alaoui K. Mir-31 is a broad regulator of beta1-integrin expression and function in cancer cells. Mol Cancer Res. 2011;9(11):1500–8.
Liu J, Huang J, He Y, Liu J, Liao B, Liao G. Genetic variants in the integrin gene predicted microRNA-binding sites were associated with the risk of prostate cancer. Mol Carcinog. 2014;53(4):280–5.
Pylayeva Y, Gillen KM, Gerald W, Beggs HE, Reichardt LF, Giancotti FG. Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling. J Clin Invest. 2009;119(2):252–66.
Japanese Gastric Cancer A. Japanese classification of gastric carcinoma—2nd English edition. Gastric Cancer. 1998;1(1):10–24.
M PN. World Medical Association publishes the revised Declaration of Helsinki. Natl Med J India. 2014;27(1):56.
Kong X, Li G, Yuan Y, He Y, Wu X, Zhang W, et al. MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression. PLoS ONE. 2012;7(8), e41523.
Feng J, Huang C, Diao X, Fan M, Wang P, Xiao Y, et al. Screening biomarkers of prostate cancer by integrating microRNA and mRNA microarrays. Genet Test Mol Biomarkers. 2013;17(11):807–13.
Tong BD, Xiao MY, Zeng JX, Xiong W. MiRNA-21 promotes fibrosis in orbital fibroblasts from thyroid-associated ophthalmopathy. Mol Vis. 2015;21:324–34.
Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y, et al. Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun. 2008;377(1):114–9.
Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10(1):9–22.
Ohyagi-Hara C, Sawada K, Kamiura S, Tomita Y, Isobe A, Hashimoto K, et al. Mir-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin alpha5 expression. Am J Pathol. 2013;182(5):1876–89.
Liu JF, Zhou XK, Chen JH, Yi G, Chen HG, Ba MC, et al. Up-regulation of PIK3CA promotes metastasis in gastric carcinoma. World J Gastroenterol. 2010;16(39):4986–91.
Lynam-Lennon N, Reynolds JV, Marignol L, Sheils OM, Pidgeon GP, Maher SG. MicroRNA-31 modulates tumour sensitivity to radiation in oesophageal adenocarcinoma. J Mol Med (Berl). 2012;90(12):1449–58.
Kim HS, Lee KS, Bae HJ, Eun JW, Shen Q, Park SJ, et al. MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer. Oncotarget. 2015;6(10):8089–102.
Wang S, Li Q, Wang K, Dai Y, Yang J, Xue S, et al. Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer. Clin Transl Oncol. 2013;15(10):849–54.
Acknowledgments
We would like to acknowledge the reviewers for their helpful comments on this paper.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the Ethical Committee of Department of Endoscopics, China-Japan Union Hospital of Jilin University. Written informed consents were obtained from all study subjects and/or their legal guardians. This study complied with the guidelines and principles of the Declaration of Helsinki.
Conflicts of interests
None
Additional information
This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010"
About this article
Cite this article
Zhang, XB., Song, L., Wen, HJ. et al. RETRACTED ARTICLE: Upregulation of microRNA-31 targeting integrin α5 suppresses tumor cell invasion and metastasis by indirectly regulating PI3K/AKT pathway in human gastric cancer SGC7901 cells. Tumor Biol. 37, 8317–8325 (2016). https://doi.org/10.1007/s13277-015-4511-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4511-y