The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy

Abstract

Hepatocellular carcinomas (HCC) are commonly diagnosed at an advanced stage with unresectable tumors. Although numerous non-surgical approaches have been developed to treat HCC, the prognosis of patients with HCC is still poor. This study investigated the expression of miR-149 and PARP-2 in HCC tumor tissues and their roles in sensitizing chemo/radiotherapy. The expression of miR-149 was measured by real-time PCR, and PARP-2 protein was measured by immunohistochemistry and Western blot. The xenograft HCC mouse model was established by inoculating Hep G2 cells. Increased PARP-1 and decreased miR-149 expression was observed in HCC tissues compared to peritumoral tissues. Positive PARP-2 and low miR-149 expression correlated with larger tumor mass size (P < 0.001), capsular and vascular invasion (P < 0.001), lymph node metastasis (P = 0.02), high histological grade (P < 0.001), TNM (P < 0.001), and BCLC grade (P = 0.001). The Kaplan-Meier survival analysis showed a negative correlation between high PARP-2 expression or low miR-149 expression in HCC tissues with the survival of patients. High PARP-2 and low miR-149 correlated with a low 5-year survival rate and are poor prognosis factors. Overexpression of miR-149 or inhibition of PARP-2 expression could inhibit tumor growth but was more effective in sensitizing chemotherapy and radiotherapy in xenograft HCC animal models. Increased PARP-2 expression and loss of miR-149 expression are involved in the pathogenesis of HCC and are poor prognosis factors in patients with HCC. Although both miR-149 overexpression and PARP-2 inhibitor exert some antitumoral effect, PARP-2 inhibitor is a chemo/radio sensor and can be used to enhance chemotherapy and radiotherapy in patients with HCC.

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