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A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.

ABSTRACT: The Hippo pathway plays an important role in the development of hepatocellular carcinoma (HCC). The present study aimed at exploring the genetic variants of Hippo pathway-related genes and their association with HCC prognosis. A total of 331 HCC patients who tested positive for hepatitis B surface antigen were recruited in this study. None of the patients had prior surgical treatment. Twelve potentially functional single-nucleotide polymorphisms (rs7317471 and rs9509492 in LATS2; rs4810446, rs2267853, rs8000, and rs6073627 in MST1; rs10955176 in MST2; and rs16861979, rs2043550, rs16861985, rs1055153, and rs7630434 in TAZ) in the Hippo pathway were genotyped from patients' peripheral leukocytes using the Sequenom MassARRAY iPLEX platform. Cox proportional hazard models and log-rank test were used for the survival analyses. LATS2 rs7317471 C>T polymorphism was significantly associated with decreased risk of death in HCC using the dominant model (adjusted hazard ratio [HR] =0.63, 95% confidence interval [CI] =0.46-0.87, P=0.004). Furthermore, using stratified analysis, LATS2 rs7317471 CT/TT genotypes were found to be significantly associated with decreased risk of death in patients who were below 53 years of age (adjusted HR =0.50), females (adjusted HR =0.60), smokers (adjusted HR =0.56), drinkers (adjusted HR =0.58), have Barcelona clinic liver cancer stage B (adjusted HR =0.62), and received no prior chemotherapy or transcatheter hepatic arterial chemoembolization (adjusted HR =0.48). Our results suggested that LATS2 rs7317471 could be used as a potential biomarker for the prediction of HCC prognosis.

SUBMITTER: Shen L

PROVIDER: S-EPMC4831600 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.

Shen Lili L Wen Juan J Zhao Tingting T Hu Zhibin Z Song Ci C Gu Dongying D He Mingliang M He Mingliang M Lee Nikki P NP Xu Zhi Z Chen Jinfei J

OncoTargets and therapy 20160404

The Hippo pathway plays an important role in the development of hepatocellular carcinoma (HCC). The present study aimed at exploring the genetic variants of Hippo pathway-related genes and their association with HCC prognosis. A total of 331 HCC patients who tested positive for hepatitis B surface antigen were recruited in this study. None of the patients had prior surgical treatment. Twelve potentially functional single-nucleotide polymorphisms (rs7317471 and rs9509492 in LATS2; rs4810446, rs22 ...[more]

PMID: 27110123

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Project description:Background:Sustained proliferation and active metastasis are hallmarks of cancer, and they pose major challenges to the development of treatments and a cure for hepatocellular carcinoma (HCC). Thus, the mechanisms of proliferation, migration, and invasion of cancer cells need to be investigated. Many studies indicate that dysregulation of microRNA plays important roles in the progression of HCC, but the role of placenta-specific microRNA (miR-512-3p) in HCC has not been systematically investigated. Purpose:In the current study, the expression, biological function, and mechanisms of miR-512-3p involvement in HCC were investigated. Methods:Real-time quantitative polymerase chain reaction assays were conducted to determine miR-512-3p levels in HCC tissues and cell lines. The StarBase V3.0 online platform was used to compare miR-512-3p levels in HCC tissues with TCGA data and to identify potential miR-512-3p target genes. Associations between miR-512-3p and clinicopathological characteristics were analyzed statistically. MTT, ethynyl deoxyuridine, and transwell assays were performed to assess cell viability, proliferation, migration, and invasion. The luciferase reporter gene assay was used to verify target genes. Recuse assays were performed to confirm whether large tumor suppressor kinase 2 (LATS2) participated in the regulatory effects of miR-512-3p on HCC cell proliferation and motility, and whether miR-512-3p mediated the tumor-promoting effects of hypoxia. Results:miR-512-3p was upregulated in HCC and it was associated with worse survival and unfavorable clinicopathological characteristics. Functional assays indicated that miR-512-3p contributed to HCC cell proliferation, migration, and invasion. Mechanistically, LATS2-a downstream target of miR-512-3p-mediated the tumor-promoting effects of miR-512-3p in HCC. Hypoxia could elevate miR-512-3p levels in HCC cells, and miR-512-3p partially mediated the tumor-promoting effects of hypoxia. Conclusion:Hypoxia-induced miR-512-3p contributes to HCC cell proliferation, migration, and invasion by targeting LATS2 and inhibiting the Hippo/yes-associated protein 1 pathways.

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A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.

Publications

A genetic variant in large tumor suppressor kinase 2 of Hippo signaling pathway contributes to prognosis of hepatocellular carcinoma.

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