miR-365 inhibited the proliferation and tumorigenicity of gastric cancer cells by targeting E2F2

doi:10.3969/j.issn.1006-7795.2016.01.001

Abstract

Abstract: Objective To investigate the regulatory role of miR-365 on proliferation and tumorigenicity of gastric cancer cells, and explore the functional mechanism of miR-365 by verifying its target molecule E2F2 protein. Methods The expression profile of miR-365 in mouse tissues was checked by Northern blotting. The expression of miR-365 in human gastric cancer tissues was detected by Real-Time PCR. The regulatory role of miR-365 on gastric cancer cell proliferation and tumorigenicity were explored with cells experiment and nude mouse tumorigenicity assay; The potential binding site of miR-365 in the E2F2 3' untranslated region (3'UTR) was predicted with the bioinformatic tools; The luciferase report plasmids containing the wild type and mutated binding site of E2F2 3'UTR were constructed, and were used to study the regulation mechanism and identify the binding sites of miR-365 by luciferase activity analysis; The regulation effect of miR-365 on E2F2 protein expression was checked by Western blotting. Results The specific expression of miR-365 was detected in various digestive tissues including stomach; miR-365 was down-regulated in human gastric cancer tissues; miR-365 inhibited the expression of E2F2 protein by recognizing the specific binding site on the 3'UTR of E2F2 mRNA. Conclusion miR-365 was down-regulated in gastric cancer tissues of human and mouse model, and suppressed the proliferation and tumorigenicity of gastric cancer cells by inhibiting the expression of E2F2.

Key words: E2F2, miR-365, gastric cancer, microRNA

CLC Number:

R735.2

Guo Shuilong, Zhu Shengtao, Cheng Rui, Shao Linlin, Sun Xiumei, Zhang Shutian. miR-365 inhibited the proliferation and tumorigenicity of gastric cancer cells by targeting E2F2[J]. Journal of Capital Medical University, 2016, 37(1): 1-5.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2016.01.001

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2016/V37/I1/1

References

[1] Kamangar F, Dores G M, Anderson W F. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world[J]. J Clin Oncol, 2006, 24(14): 2137-2150.
[2] Yang L. Incidence and mortality of gastric cancer in China[J]. World J Gastroenterol, 2006, 12(1): 17-20.
[3] Guo S L, Ye H, Teng Y, et al. Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency[J]. Nat Commun, 2013, 4: 2544.
[4] Zhou X, Xu X, Wang J, et al. Identifying miRNA/mRNA negative regulation pairs in colorectal cancer[J]. Sci Rep, 2015, 5: 12995.
[5] Nie J, Liu L, Zheng W, et al. microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2[J]. Carcinogenesis, 2012, 33(1): 220-225.
[6] Indovina P, Pentimalli F, Casini N, et al. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy[J]. Oncotarget, 2015, 6(20): 17873-17890.
[7] Xanthoulis A, Tiniakos D G. E2F transcription factors and digestive system malignancies: how much do we know?[J]. World J Gastroenterol, 2013, 19(21): 3189-3198.
[8] Sun Q, Zhang Y, Yang G, et al. Transforming growth factor-beta-regulated miR-24 promotes skeletal muscle differentiation[J]. Nucleic Acids Res, 2008, 36(8): 2690-2699.
[9] Liu J, Zhang L, Lei J, et al. MicroRNA-responsive cancer cell imaging and therapy with functionalized gold nanoprobe[J]. ACS Appl Mater Interfaces, 2015, 7(34): 19016-19023.
[10] Zhang Z, Li Z, Li Y, et al. MicroRNA and signaling pathways in gastric cancer[J]. Cancer Gene Ther, 2014, 21(8): 305-316.
[11] Bai J, Zhang Z, Li X, et al. MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression[J]. Cancer Biomark, 2015, 15(5): 599-608.
[12] Bai J, Zhang Z, Li X, et al. MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression[J]. Int J Clin Exp Pathol, 2015, 8(5): 4913-4922.
[13] Chen Z, Huang Z, Ye Q, et al. Prognostic significance and anti-proliferation effect of microRNA-365 in hepatocellular carcinoma[J]. Int J Clin Exp Pathol, 2015, 8(2): 1705-1711.
[14] Kang S M, Lee H J, Cho J Y. MicroRNA-365 regulates NKX2-1, a key mediator of lung cancer[J]. Cancer Lett, 2013, 335(2): 487-494.
[15] Evangelou K, Havaki S, Kotsinas A. E2F transcription factors and digestive system malignancies: how much do we know?[J]. World J Gastroenterol, 2014, 20(29): 10212-10216.
[16] Iglesias-Ara A,Zenarruzabeitia O, Buelta L, et al. E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution[J]. Cell Death Differ, 2015, 22(10): 1577-1589.
[17] Zhang P, Zheng C, Ye H, et al. MicroRNA-365 inhibits vascular smooth muscle cell proliferation through targeting cyclin D1[J]. Int J Med Sci, 2014, 11(8): 765-770.
[18] Zhou L, Wang Y, Ou C, et al. microRNA-365-targeted nuclear factor I/B transcriptionally represses cyclin-dependent kinase 6 and 4 to inhibit the progression of cutaneous squamous cell carcinoma[J]. Int J Biochem Cell Biol, 2015, 65: 182-191.
[19] Guo S L, Ye H, Teng Y, et al. Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency[J]. Nat Commun, 2013, 4: 2544.
[20] Tong F, Cao P, Yin Y, et al. MicroRNAs in gastric cancer: from benchtop to bedside[J]. Dig Dis Sci, 2014, 59(1): 24-30.
[21] Kanat O, O'Neil B, Shahda S. Targeted therapy for advanced gastric cancer: A review of current status and future prospects[J]. World J Gastrointest Oncol, 2015, 7(12): 401-410.
[22] 李龙,李静,黄东兰,等. 胃癌患病风险关键基因筛选[J]. 中华肿瘤防治杂志,2014,21(2):95-99.
[23] 李立平,吴炜景,赵亚刚. microRNA与胃癌的研究进展[J]. 中华肿瘤防治杂志. 2013,20(4):312-316.