The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy.
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.
National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 41008, China.
Ling
L
Lin
National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 41008, China.
Yang-de
YD
Zhang
Department of Anestesiology, Hunan Cancer Hospital (the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University), Changsha, Hunan, 410013, China.
Zi-Yu
ZY
Chen
National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 41008, China. Chenyx008@aliyun.com.
Yuxiang
Y
Chen
Cancer Research Institute, Xiangya School of Medicine, Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Central South University, 110 Xiangya Road, Changsha, Hunan, 410008, China. rencaiping@csu.edu.cn.
Cai-Ping
CP
Ren
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C551557:MIRN149 microRNA, human; D035683:MicroRNAs; C483041:PARP2 protein, human; D011065:Poly(ADP-ribose) Polymerases
Chemotherapy; Hepatocellular carcinoma; PARP-2; Prognosis; Radiotherapy; miR-149