miR-192, a prognostic indicator, targets the SLC39A6/SNAIL pathway to reduce tumor metastasis in human hepatocellular carcinoma
Year: 2015
Type: article
Abstract: // Junwei Lian 1, * , Ying Jing 1, * , Qiongzhu Dong 2, 3, * , Lin Huan 1 , Di Chen 1 , Chunyang Bao 4 , Qifeng Wang 4 , Fangyu Zhao 1 , Jinjun Li 1 , Ming Yao 1 , Lunxiu Qin 2, 3, 5 , Linhui Liang 2, 4 , Xianghuo He 1, 2, 4 1 State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China 2 Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200032, China 4 Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China 5 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China * These authors contributed equally to this work Correspondence to: Xianghuo He, e-mail: [email protected] Linhui Liang, e-mail: [email protected] Lunxiu Qin, e-mail: [email protected] Keywords: miR-192, SLC39A6, metastasis, prognosis, hepatocellular carcinoma Received: April 24, 2015 Accepted: November 20, 2015 Published: December 14, 2015 ABSTRACT Metastasis is one of the causes of cancer death. Functions and mechanisms of microRNAs (miRNAs) involved in hepatocellular carcinoma (HCC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in MHCC-97L, MHCC-97H and HCC-LM3 cells with gradually increasing metastatic potential to disclose crucial miRNAs involved in HCC metastasis. miR-192 expression decreased and negatively correlated with vascular invasion in HCC specimens. Gain and loss of function studies revealed that miR-192 significantly suppressed metastasis of HCC cells in vitro and in vivo . Solute carrier family 39 member 6 (SLC39A6) was identified as a direct and functional target of miR-192. In addition, SLC39A6 negatively correlated with miR-192 in HCC samples and promoted HCC cell migration and invasion. Moreover, miR-192 decreased SLC39A6 expression, subsequently downregulating SNAIL and upregulating E-cadherin expression. Suppression of migration and invasion caused by miR-192 overexpression was alleviated by exogenous Snail expression. Intriguingly, lower miR-192 expression and higher SLC39A6 expression significantly contributed to poorer outcomes in HCC patients. Multivariate analysis indicated that miR-192 was an independent and significant predictor of HCC patient overall survival. In conclusion, we newly determined that miR-192 targeted the SLC39A6/SNAIL pathway to reduce tumor metastasis in HCC cells. This axis provided insights into the mechanism underlying miRNA regulation of HCC metastasis and a novel therapeutic target for HCC treatment.
Source: Oncotarget
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2276285019