Abstract
Liver cancer is one of leading causes of cancer-related deaths. A deeper mechanistic understanding of liver cancer could lead to the development of more effective therapeutic strategies. In our previous work, we screened 646 miRNAs and identified 11 that regulate liver cancer cell migration. The current study shows that miR-525-3p is frequently up-regulated in liver cancer tissues, and enhanced expression of miR-525-3p can promote liver cancer cell migration and invasion. Zinc finger protein 395 (ZNF395) is the direct functional target gene for miR-525-3p, and it is frequently down-regulated in liver cancer tissues. High expression of ZNF395 can significantly inhibit while knockdown of ZNF395 expression can markedly enhance the migration and invasion of liver cancer cells, suggesting that ZNF395 suppresses metastasis in liver cancer. Down-regulation of ZNF395 can mediate miR-525-3p induced liver cancer cell migration and invasion. In conclusion, miR-525-3p promotes liver cancer cell migration and invasion by directly targeting ZNF395, and the fact that miR-525-3p and ZNF395 both play important roles in liver cancer progression makes them potential therapeutic targets.
Highlights
Metastases are the main cause of cancer-related death [1,2]
PRF/5,HepG2, SK-HEP-1, MCF7, A549, NCI-H460, Tera-1 and Tera-2 were purchased from ATCC; HuH-7 was purchased from Japanese Collection of Research Bioresources (JCRB), SMMC-7721 and BEL-7402 were purchased from Typical culture preservation commission cell bank, Chinese academy of sciences (NCB); MHCC-97L and LM3 were gifts from Zhongshan Hospital, Fudan University (Shanghai, China); SMMC-7721, BEL-7402, MHCC-97L and LM3 used in this study have been described in previous publication [24,30,31,32]
To explore the role of miR-525-3p in liver cancer development, the expression level of miR-525-3p was detected in 136 liver cancer and paired adjacent noncancerous liver tissues (NT). miR525-3p was significantly up-regulated in liver cancer tissues (Figure 1A), with up-regulation observed in 60% of liver cancer tissues (Figure 1B)
Summary
Metastases are the main cause of cancer-related death [1,2]. Systematically studying the molecular mechanisms of liver cancer metastasis is important for the development of new therapeutic strategies. Tumor metastasis is a multi-stage complex process in which tumor cells move to surrounding or distant tissues after breaking away from the primary tumor. This process involves tumor cell transit through the extracellular matrix (ECM) and the basement membrane of the local blood vessel [3,4,5,6,7], followed by movement into the host microenvironment [8,9,10]. Recent studies have found that in addition to protein coding genes, noncoding RNAs such as miRNAs play important regulatory roles in the process of metastasis [11,12,13,14,15,16]. Hypoxia-inducible expression of miR-210 regulates VMP1-mediated hypoxia-induced liver cancer cell metastasis [26]
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