MicroRNA-101-3p regulates gastric cancer cell proliferation, invasion and apoptosis by targeting PIM 1 expression

Fubing Wu; Wen Huang; Lili Yang; Fanggui Xu

doi:10.14715/cmb/2019.65.7.20

Issue

Vol. 65 No. 7: Issue 7

Issue Published : October 14, 2019

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

MicroRNA-101-3p regulates gastric cancer cell proliferation, invasion and apoptosis by targeting PIM 1 expression

https://doi.org/10.14715/cmb/2019.65.7.20

Fubing Wu

Department of Oncology, Sin Run Run Hospital of Nanjing Medical Unversity, Nanjing 210000, Jiangsu Province, China

Wen Huang

Department of Oncology, Nanjing Pukou Hospital, Nanjing 210000, Jiangsu Province, China

Lili Yang

Department of Oncology, Nanjing Second Hospital, Nanjing 210000, Jiangsu Province, China

Fanggui Xu

Department of General Surgery, Sin Run Run Hospital of Nanjing Medical Unversity, Nanjing 210000, Jiangsu Province, China

Corresponding Author(s) : Fanggui Xu

vpae17@163.com

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7
Article Published : September 30, 2019

Abstract

To investigate the effect of microRNA-101-3p (miRNA-101-3p) on proliferation, invasion and apoptosis of gastric cancer (GC) cells, and to explore its influence mechanism. Human GC cell line (AGS) and normal human gastric epithelial cell line (GES-1) were used in this study. The cells were transfected with proto-oncogene serine/threonine-protein kinase (PIM 1) overexpression plasmid, miRNA-101-3p mimics, or miRNA-101-3p non-homologous sequence using lipofectamine 2000. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the expressions of miRNA-101-3p and PIM 1 in GC cells. Cell counting kit-8 (CCK-8) and Transwell assays were used to assess the effect of miRNA-101-3p on proliferation and invasion of GC cells. The regulatory effect of miRNA-101-3p on PIM 1 was assessed using bioinformatics analysis and luciferase reporter gene assay. The expression of miRNA-101-3p was significantly down-regulated in GC cells, relative to normal human gastric epithelial cells (p < 0.05). However, the expression of PIM 1 mRNA was significantly upregulated in GC cells, when compared with normal gastric epithelial cells (p < 0.05). The expression level of miRNA-101-3p was significantly higher in miRNA-101-3p mimic group than in miRNA-101-3p control and normal control groups (p < 0.05). Cell proliferation in miRNA-101-3p mimic group was significantly and time-dependently reduced, when compared with miRNA-101-3p control and normal control groups (p < 0.05). Transfection with miRNA-101-3p mimics significantly increased the invasiveness of AGS cells, and significantly promoted their apoptosis (p < 0.05). Results of qRT-PCR and Western blotting showed that increased miRNA-101-3p expression significantly reduced the expression of PIM 1, while decreased miRNA-101-3p expression promoted the expression of PIM 1 (p < 0.05). Results of bioinformatics showed that miRNA-101-3p had specific binding sequence in the 3'UTR region of PIM 1. Cloning of miRNA-101-3p sequence into the luciferase reporter plasmid led to significant inhibition of the expression of PIM 1 (p < 0.05), but had no inhibitory effect on mutated PIM 1 3'UTR (p > 0.05). Overexpression of PIM 1 significantly reversed the inhibition of proliferation and invasion, and promotion of apoptosis by miRNA-101-3p (p < 0.05). These results indicate that miRNA-101-3p inhibits the proliferation and invasion of GC cells, and promotes their apoptosis by regulation of the expression of PIM-1.

Keywords

Gastric cancer MicroRNA-101-3p Proliferation Invasion Apoptosis.

Wu, F., Huang, W., Yang, L., & Xu, F. (2019). MicroRNA-101-3p regulates gastric cancer cell proliferation, invasion and apoptosis by targeting PIM 1 expression. Cellular and Molecular Biology, 65(7), 118–122. https://doi.org/10.14715/cmb/2019.65.7.20

Download Citation

References

Hassanalilou T, Ghavamzadeh S, Khalili L. Curcumin and gastric cancer: a review on mechanisms of action. J Gastrointest Cancer 2019; 50: 185-192.
Zhu XL, Ren LF, Wang HP. Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer. World J Gastroenterol 2019; 25: 1580-1591.
Masood N, Basharat Z, Khan T, Yasmin A. Entangling relation of Micro RNA-let7, miRNA-200 and miRNA-125 with various cancers. Pathol Oncol Res 2017; 23: 707-715.
Yang X, Pang YY, He RQ, Lin P, Cen JM, Yang H, et al. Diagnostic value of strand-specific miRNA-101-3p and miRNA-101-5p for hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism of action. FEBS OPEN BIO 2018; 8: 64-84.
Wang H, Wang L, Zhang G, Lu C, Chu H, Yang R, et al. MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer. Oncotarget 2018; 9: 7501-7512.
Meng Q, Yang BY, Liu B, Yang JX, Sun Y. Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p. Int J Biol Markers 2018; 33: 148-155.
Wang C, Liu B. miR-101-3p induces autophagy in endometrial carcinoma cells by targeting EZH2. Arch Gynecol Obstet 2018; 297: 1539-1548.
Wu X, Zhou J, Wu Z, Chen C, Liu J, Wu G. MiR-101-3p suppresses HOX transcript antisense RNA (HOTAIR)-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells. Oncol Res 2017; 25: 1383-1390.
Ren K, Liu QQ, An ZF, Zhang DP, Chen XH. MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer. Eur Rev Med Pharmacol Sci 2017; 21: 3028-3037.
Kim JH, Lee DK, Kim J, Choi S, Park W, Ha KS. A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. Cell Death Dis 2017; 8: 2808.
Xiong W, Ran J, Jiang R, Guo P, Shi X, Li H, et al. miRNA-320a inhibits glioma cell invasion and migration by directly targeting aquaporin 4. Curr Oncol Rep 2018; 39: 1939-1947.
Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009; 361: 1437-1447.
Liu P, Ye F, Xie X, Li X, Tang H, Li S, et al. mir-101-3p is a key regulator of tumor metabolism in triple negative breast cancer targeting AMPK. Oncotarget 2016; 7: 35188-35198.
Zhang X, He X, Liu Y, Zhang H, Chen H, Guo S, et al. MiR-101-3p inhibits the growth and metastasis of non-small cell lung cancer through blocking PI3K/AKT signal pathway by targeting MALAT-1. Biomed Pharmacother 2017; 93: 1065-1073.
Wang Z, Bhattacharya N, Weaver M, Petersen K, Meyer M, Gapter L, et al. Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. J Vet Sci 2001; 2: 167-179.
Liu K, Gao H, Wang Q, Wang L, Zhang B, Han Z, et al. Hispidulin suppresses cell growth and metastasis by targeting PIM1 through JAK2/STAT3 signaling in colorectal cancer. Cancer Sci 2018; 109: 1369-1381.
Zhao W, Qiu R, Li P, Yang J. PIM1: a promising target in patients with triple-negative breast cancer. Med Oncol 2017; 34: 142-149.
Xu J, Zhu X, Li Q, Chen C, Guo Z, Tan Z, et al. Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC). Cancer Cell Int 2018; 18: 22-28.

References

Hassanalilou T, Ghavamzadeh S, Khalili L. Curcumin and gastric cancer: a review on mechanisms of action. J Gastrointest Cancer 2019; 50: 185-192.

Zhu XL, Ren LF, Wang HP. Plasma microRNAs as potential new biomarkers for early detection of early gastric cancer. World J Gastroenterol 2019; 25: 1580-1591.

Masood N, Basharat Z, Khan T, Yasmin A. Entangling relation of Micro RNA-let7, miRNA-200 and miRNA-125 with various cancers. Pathol Oncol Res 2017; 23: 707-715.

Yang X, Pang YY, He RQ, Lin P, Cen JM, Yang H, et al. Diagnostic value of strand-specific miRNA-101-3p and miRNA-101-5p for hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism of action. FEBS OPEN BIO 2018; 8: 64-84.

Wang H, Wang L, Zhang G, Lu C, Chu H, Yang R, et al. MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer. Oncotarget 2018; 9: 7501-7512.

Meng Q, Yang BY, Liu B, Yang JX, Sun Y. Long non-coding RNA SNHG6 promotes glioma tumorigenesis by sponging miR-101-3p. Int J Biol Markers 2018; 33: 148-155.

Wang C, Liu B. miR-101-3p induces autophagy in endometrial carcinoma cells by targeting EZH2. Arch Gynecol Obstet 2018; 297: 1539-1548.

Wu X, Zhou J, Wu Z, Chen C, Liu J, Wu G. MiR-101-3p suppresses HOX transcript antisense RNA (HOTAIR)-induced proliferation and invasion through directly targeting SRF in gastric carcinoma cells. Oncol Res 2017; 25: 1383-1390.

Ren K, Liu QQ, An ZF, Zhang DP, Chen XH. MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer. Eur Rev Med Pharmacol Sci 2017; 21: 3028-3037.

Kim JH, Lee DK, Kim J, Choi S, Park W, Ha KS. A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. Cell Death Dis 2017; 8: 2808.

Xiong W, Ran J, Jiang R, Guo P, Shi X, Li H, et al. miRNA-320a inhibits glioma cell invasion and migration by directly targeting aquaporin 4. Curr Oncol Rep 2018; 39: 1939-1947.

Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, et al. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009; 361: 1437-1447.

Liu P, Ye F, Xie X, Li X, Tang H, Li S, et al. mir-101-3p is a key regulator of tumor metabolism in triple negative breast cancer targeting AMPK. Oncotarget 2016; 7: 35188-35198.

Zhang X, He X, Liu Y, Zhang H, Chen H, Guo S, et al. MiR-101-3p inhibits the growth and metastasis of non-small cell lung cancer through blocking PI3K/AKT signal pathway by targeting MALAT-1. Biomed Pharmacother 2017; 93: 1065-1073.

Wang Z, Bhattacharya N, Weaver M, Petersen K, Meyer M, Gapter L, et al. Pim-1: a serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis. J Vet Sci 2001; 2: 167-179.

Liu K, Gao H, Wang Q, Wang L, Zhang B, Han Z, et al. Hispidulin suppresses cell growth and metastasis by targeting PIM1 through JAK2/STAT3 signaling in colorectal cancer. Cancer Sci 2018; 109: 1369-1381.

Zhao W, Qiu R, Li P, Yang J. PIM1: a promising target in patients with triple-negative breast cancer. Med Oncol 2017; 34: 142-149.

Xu J, Zhu X, Li Q, Chen C, Guo Z, Tan Z, et al. Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC). Cancer Cell Int 2018; 18: 22-28.

Author biographies is not available.