The mechanism of miR-181a inhibiting invasion and migration of salivary adenoid cystic carcinoma: an in vitro study

Abstract

Abstract: PURPOSE: To investigate the effect of miR-181a on invasion and migration in salivary adenoid cystic carcinoma (SACC). METHODS: QRT-PCR analysis was used to detect the expression of miR-181a in the paired SACC cell lines with different invasive and migration ability. The SACC cell lines SACC-LM and SACC-83 were transfected with miR-181a mimics and miR-181a LNA, respectively. Confocal microscopy was used to observe the changes of cytoskeleton after transfection. Western blot analysis was performed to demonstrate the invasion and metastasis related genes after transfection. Lung metastasis model in nude mice was established to analyze the effect of miR-181a on lung metastatic ability of SACC cell lines after transfection. The data was analyzed using SPSS 17.0 software package. RESULTS: QRT-PCR analysis showed that low invasive and migration ability cell line (SACC-83) expressed higher miR-181a than higher invasive and migration ability cell line (SACC-LM). Ectopic transfection of the miR-181a mimics to the SACC-LM cells led to decreased gene expression of Slug, pERK1/2, ERK1/2 and cells turned to be spindle. When the SACC-83 cells were treated with miR-181a LNA, the gene expression of Slug, pERK1/2, ERK1/2 increased and cells turned to be round. Lung metastasis model in nude mice showed that compared with the mimics NC group, lung metastatic lesion size of miR-181a mimics group was significantly smaller (P<0.05). CONCLUSIONS: miR-181a can suppress the invasion and metastasis of SACC.

Key words: miR-181a, Salivary adenoid cystic carcinoma, Invasion, Metastasis

CLC Number:

R739.87

HE Qian-ting, LIU Zhong-hua, ZHAO Luo-dan, ZHAO Ting-ting, WANG An-xun. The mechanism of miR-181a inhibiting invasion and migration of salivary adenoid cystic carcinoma: an in vitro study[J]. China Journal of Oral and Maxillofacial Surgery, 2015, 13(1): 11-15.

References

[1] Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of salivary origin. A clinicopathologic study of 242 cases [J]. Am J Surg, 1974, 128(4): 512-520.
[2] Bradley PJ. Adenoid cystic carcinoma of the head and neck: a review [J]. Curr Opin Otolaryngol Head Neck Surg, 2004, 12(2): 127-132.
[3] Huang M, Ma D, Sun K, et al. Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands [J]. Int J Oral Maxillofac Surg, 1997, 26(6): 435-439.
[4] Sung MW, Kim KH, Kim JW, et al. Clinicopathologic predictors and impact of distant metastasis from adenoid cystic carcinoma of the head and neck [J]. Arch Otolaryngol Head Neck Surg, 2003, 129(11): 1193-1197.
[5] Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil′ hypothesis revisited [J]. Nat Rev Cancer, 2003, 3(6): 453-458.
[6] Filder IJ. Critical factors in the biology of human cancer metastasis:twenty-eighth G.H.A. Clowes memorial award lecture [J]. Cancer Res, 1990, 50(19): 6130-6138.
[7] Nicolson GL. Cancer metastasis: tumor cells and host-organ properties important in metastasis to specific secondary sites [J]. Biochim Biophys Acta, 1988, 984(2): 175-224.
[8] Baranwal S, Alahari SK. miRNA control of tumor cell invasion and metastasis [J]. Int J Cancer, 2010, 126(6): 1283-1290.
[9] Shi L, Cheng Z, Zhang J, et al. hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells [J]. Brain Res, 2008, 1236: 185-193.
[10] Ji J, Yamashita T, Budhu A, et al. Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells [J]. Hepatology, 2009, 50(2): 472-480.
[11] Bhattacharya SD, Garrison J, Guo H, et al. Micro-RNA-181a regulates osteopontin-dependent metastatic function in hepatocellular cancer cell lines [J]. Surgery, 2010, 148(2): 291-297.
[12] Pérez-Losada J, Sánchez-Martín M, Rodríguez-García A, et al. Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway[J]. Blood,2002,100(4): 1274-1286.
[13] Tang Y, Liang X, Zheng M, et al. Expression of c-kit and Slug correlates with invasion and metastasis of salivary adenoid cystic carcinoma [J]. Oral Oncol, 2010, 46(4): 311-316.
[14] Wang C, Liu X, Huang H, et al. Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma [J]. Int J Cancer, 2012, 130(10): 2249-2258.
[15] Adeyinka A, Nui Y, Cherlet T, et al. Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression [J]. Clin Cancer Res, 2002, 8(6): 1747-1753.
[16] Chen H, Zhu G, Li Y, et al. Extracellular signal-regulated kinase signaling pathway regulates breast cancer cell migration by maintaining slug expression [J]. Cancer Res, 2009, 69(24): 9228-9235.