HIWI is associated with prognosis in patients with hepatocellular carcinoma after curative resection

Abstract

BACKGROUND: PIWI protein family was found to play an important role in stem cell self-renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n ¼ 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n ¼ 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up-regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P ¼ .047) and intrahepatic metastasis (P ¼ .027) and was an independent risk factor for overall survival (P ¼ .007) and recurrence-free survival (P ¼ .036), particularly in patients with low serum afetoprotein and low Edmondson-Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well-differentiated HCC.

PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses

“…PIWI family proteins have been shown to be aberrantly expressed and associated with poor prognosis in ovarian, colorectal, gastric, hepatocellular, esophageal, and pancreatic cancers (13)(14)(15)(16)(17)(18), and piRNA expression has been observed in bladder, colon, lung, cervical, breast, hepatocellular, and gastric cancers (19)(20)(21)(22)(23)(24). Our recent study also identified a genetic variant in a mature piRNA sequence that is associated with breast cancer risk (25).…”

Silencing HIWI suppresses the growth, invasion and migration of glioma cells

“…in addition to the function of HiWi as a potent growth regulator, another study revealed that low levels of expression of HIWI led to a significant decrease in the migration and invasion of hepatocellular carcinoma cells (16). The invasion of glioma cells into brain tissue is a pathologic hallmark of World Health organization (WHo) grade Ⅱ-Ⅳ gliomas, which contributes significantly to the failure of current treatments (28).…”

“…Small interfering rna against HiWi and a negative control (scrambled control) were purchased from genePharma (Shanghai, China). The following sirna sequences described previously (16) were used: HIWI, 5'-GCC guucauacaagacuaatt-3'; negative control, 5'-uuc uccgaacgugucacgutt-3'. transfection was performed using lipofectamine 2000 reagent (invitrogen life technologies, Carlsbad, CA, USA) according to the manufacturer's instructions.…”

Overexpression of Hiwi Promotes Growth of Human Breast Cancer Cells

“…Quantitative real-time RT-PCR (RT-qPCR) was performed using a SYBR PrimeScript RT-qPCR Kit (TaKaRa Bio Inc., Tokyo, Japan) according to the kit mannual, with β-actin as an internal control. The primers for hiwi and β-actin were synthesized by Shanghai Sangon company (Shanghai, China) according to rhe reported sequences (Zhao et al, 2012). The RT-qPCR was performed with a Lightcycler 480 II (Roche, Mannheim, Germany).…”