Hepatocellular carcinoma (HCC) accounts for 70-85% of primary liver cancers and ranks as the second leading cause of cancer-related deaths among males worldwide (1). HCC usually develops in cirrhotic livers secondary to viral infections

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of proteins that functions by maintaining the repressive transcriptional states of many developmental regulatory genes. In addition, it has been shown that miR-195 plays an important role in the molecular etiology of HCC; however, the effect and possible mechanism of PHF19 on HCC is unclear, and the association between PHF19 and miR-195 has seldom been addressed. In the present study, we investigated the carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our results showed that PHF19 is a potential target of hsa-miR-195-5p based on a bioinformatic analysis and results of a luciferase reporter assay. PHF19 was downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we demonstrated that overexpression of PHF19 promoted hepatoma cell migration, invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195-5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed the growth of xenograft tumors in nude mice. These results provide evidence that PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p. Introduction Hepatocellular carcinoma (HCC) accounts for 70-85% of primary liver cancers and ranks as the second leading cause of cancer-related deaths among males worldwide (1). HCC usually develops in cirrhotic livers secondary to viral infections [hepatitis B virus (HBV) and hepatitis C virus (HCV)], alcohol abuse, metabolic disorders, or carcinogenic agents (2,3). HCC has heterogeneous etiologic and molecular profiles and varied responses to therapeutics (4). This tumor diversity arises from the multistep hepatocarcinogenic processes requiring sequential genetic and epigenetic alterations, including gene mutations and/or chromosome instability (3,5,6). PHD finger protein 19 (PHF19), a component of polycomb repressive complex 2 (PRC2), encodes a member of the polycomb group (PcG) of proteins that functions by maintaining repressive transcriptional states of many developmental regulatory genes (7,8). A previous study confirmed that PHF19 is frequently upregulated in several types of cancer (7). Ghislin et al (9) reported that PHF19 silencing reduced the cell proliferation rate and increased the transendothelial migration capacity of melanoma cell lines. Li et al (10) showed that the expression of PHF19 was increased in glioblastoma multiforme samples and correlated positively with astrocytoma grades. These observations suggest that PFH19 is strongly linked to aggressive tumor behavior and are in agreement with increased expression in various human tumor types. microRNAs (miRNAs) are small non-coding RNAs that control gene expression by modulating stability and/or translation of messenger RNA (mRNA) through interactions with specific sequences located in the coding or untranslated regions (UTRs) (11-13). Several studies have implicated miRNAs in a number of cancers; altered miRNA levels can result in the aberrant expression of gene products that may contribute to carcinogenesis (14-16). Recently, miR-195 was shown to be downregulated in a variety of cancers, including liver, gastric, bladder, breast and adrenocortical cancers (17-20). Introduction of miR-195 markedly suppresses colony formation in vitro and tumor development in nude mice (20). In vitro data suggest that miR-195 suppressed tumorigenicity and regulates the G1/S transition of human HCC cells (17); however, the mechanism underlying miR-195 on tumor development and the association MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma HUI XU1,2*, YAN-WeI HU1*, JIA-YI ZHAO1, XIU-MeI HU1, SHU-FeN LI1, YAN-ChAO WANG1, JI-JUAN GAO1, YAN-huA ShA1, CHUN-MIN KANG1, LI LIN1, ChuAN huANG1, JING-JING ZHAO1, LeI ZHeNG1 and QIAN WANG1 1Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515; 2Hospital of Traditional Chinese Medicine of Qingyuan City, Qingyuan, Guangdong 511500, P.R. China Received January 29, 2015; Accepted April 20, 2015 DOI: 10.3892/or.2015.3957 Correspondence to: Professor Qian Wang or Professor Lei Zheng, Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China e-mail: [email protected] e-mail: [email protected] *Contributed equally