Effect and underlying mechanism of miR-21 on proliferation and apoptosis of salivary adenoid cystic carcinoma cells

doi:10.19438/j.cjoms.2017.03.004

Abstract

Abstract: PURPOSE: To investigate the effect and regulatory mechanisms of miR-21 on proliferation and apoptosis of human salivary adenoid cystic carcinoma (SACC-LM) cells. METHODS: SACC-LM cells were transfected with miR-21 inhibitor by LipofectamineTM 2000. Meanwhile, SACC-LM cells were transfected with NC inhibitor as negative control. Cell survival rate was calculated with CCK-8 assay at 24, 48, 72 and 96 h after transfection. The apoptosis rate was measured by flow cytometry. qRT-PCR analysis and Western blot were used to detect the expression of miR-21, PDCD4 and Bcl-2 in SACC-LM cell lines after transfection. SPSS 16.0 software package was used for statistical analysis. RESULTS: miR-21 expression was remarkably downregulated in miR-21 inhibitor-transfected cells. In the meantime, gene expression of PDCD4 was increased and Bcl-2 was decreased (P<0.05). miR-21 silencing triggered to a decreased cell viability in a time-dependent manner compared with the control groups (P<0.05). The apoptosis rate was dramatically increased compared with the control groups (P<0.01), and PDCD4 protein expression was significantly increased (P<0.05), while Bcl-2 was significantly decreased (P<0.05). CONCLUSIONS: Downregulation of miR-21 can inhibit proliferation of SACC-LM cells and induce apoptosis. The mechanism may be related to the increased expression of PDCD4 and decreased expression of Bcl-2.

Key words: miR-21, Salivary adenoid cystic carcinoma, Proliferation, Apoptosis, PDCD4, Bcl-2

CLC Number:

R739.8

YAN Fei, WANG Chao, LI Ting, CAI Wen-yan, SUN Jin-hu，.. Effect and underlying mechanism of miR-21 on proliferation and apoptosis of salivary adenoid cystic carcinoma cells[J]. China Journal of Oral and Maxillofacial Surgery, 2017, 15(3): 209-213.

References

[1] 蔡文燕, 严斐, 董晶, 等辛伐他汀对唾液腺腺样囊性癌细胞生长及survivin 表达的影响[J]. 中国口腔颌面外科杂志, 2016, 14(3): 213-217.
[2] He Q, Zhou X, Li S, et al. MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway [J]. Biochim Biophys Acta, 2013, 1830(11): 5258-5266.
[3] 张瑞智, 张萍, 余波, 等. siRNA 干扰 Mcl-1对唾液腺腺样囊性癌 SACC-2细胞生物活性的影响[J]. 实用口腔医学杂志, 2014, 30(6): 809-812.
[4] He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation [J]. Nat Rev Genet, 2004, 5(7):522-531.
[5] Yu Y, Kanwar SS, Patel BB, et al. MicroRNA-21 induces stemness by downregulating transforming growth factor beta receptor 2 (TGFbetaR2) in colon cancer cells [J]. Carcinogenesis, 2012, 33(1): 68-76.
[6] Ren QH, Liang JQ, Wei JJ, et al. Epithelial and stromal expression of miRNAs during prostate cancer progression [J]. Am J Transl Res, 2014, 6(4): 329-339.
[7] 潘文征, 唐万燕, 袁伟, 等. 微小 RNA 在胰腺癌患者血浆中的表达情况及临床意义[J]. 中华肿瘤杂志, 2014, 36(5): 351-354.
[8] Faltejskova P, Besse A, Sevcikova S, et al. Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells [J]. Int J Colorectal Dis, 2012, 27(11): 1401-1408.
[9] Ren Q, Liang J, Wei J, et al. Epithelial and stromal expression of miRNAs during prostate cancer progression [J]. Am J Transl Res, 2014, 6(4): 329-339.
[10] Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma [J]. Nature, 2010, 467(7311): 86-90.
[11] Zhang BG, Li JF, Yu BQ, et al. microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN [J]. Oncol Rep, 2012, 27(4): 1019-1026.
[12] Peacock O, Lee AC, Cameron F, et al. Inflammation and MiR-21 pathways functionally interact to downregulate PDCD4 in colorectal cancer [J]. PloS One, 2014, 9(10): e110267.
[13] Shi L, Chen J, Yang J, et al. MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity [J]. Brain Res, 2010, 1352: 255-264.
[14] Li T, Li LC, Li DS, et al. MiR-34a inhibits oral cancer progression partially by repression of interleukin-6-receptor [J]. Int J Clin Exp Patho, 2015, 8(2): 1364-1373.
[15] Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes[J]. Oncogene, 2006, 25(46): 6188-6196.
[16] Najafi Z, Sharifi M, Javadi G. Degradation of miR-21 induces apoptosis and inhibits cell proliferation in human hepatocellular carcinoma [J]. Cancer Gene Ther, 2015, 22(11): 530-535.
[17] Jiang LH, Ge MH, Hou XX, et al. miR-21 regulates tumor progression through the miR-21-PDCD4-Stat3 pathway in human salivary adenoid cystic carcinoma [J]. Lab Invest, 2015, 95(12): 1398-1408.
[18] Saxena A, Shoeb M, Ramana KV, et al. Aldose reductase inhibition suppresses colon cancer cell viability by modulating microRNA-21 mediated programmed cell death 4 (PDCD4) expression [J]. Eur J Cancer, 2013, 49(15): 3311-3319.
[19] 郭民英, 邢永川, 陈卫伶, 等. Bcl-2、p53和ki-67在甲状腺癌中的表达及其临床意义的研究[J]. 现代肿瘤医学, 2014, 22(6): 1294-1297.