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A Preliminary Investigation of PVT1 on the Effect and Mechanisms of Hepatocellular Carcinoma: Evidence from Clinical Data, a Meta-Analysis of 840 Cases, and In Vivo Validation.
Zhang, Yu; Wen, Dong-Yue; Zhang, Rui; Huang, Jia-Cheng; Lin, Peng; Ren, Fang-Hui; Wang, Xiao; He, Yun; Yang, Hong; Chen, Gang; Luo, Dian-Zhong.
Afiliación
  • Zhang Y; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Wen DY; Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Zhang R; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Huang JC; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Lin P; Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Ren FH; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Wang X; Department of Orthopedics, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.
  • He Y; Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Yang H; Department of Medical Ultrasonics, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Chen G; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • Luo DZ; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Cell Physiol Biochem ; 47(6): 2216-2232, 2018.
Article en En | MEDLINE | ID: mdl-29975928
ABSTRACT
BACKGROUND/

AIMS:

Hepatocellular carcinoma (HCC) remains a difficult problem that significantly affects the survival of the afflicted patients. Accumulating evidence has demonstrated the functions of long non-coding RNA (lncRNA) in HCC. In the present study, we aimed to explore the potential roles of PVT1 in the tumorigenesis and progression of HCC.

METHODS:

In this study, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was applied to detect the differences between PVT1 expression in HCC tissues and cell lines. Then, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were searched to confirm the relationship between PVT1 expression and HCC. Moreover, a meta-analysis comprising TCGA, GEO, and RT-qPCR was applied to estimate the expression of PVT1 in HCC. Then, cell proliferation was evaluated in vitro. A chicken chorioallantoic membrane (CAM) model of HCC was constructed to measure the effect on tumorigenicity in vivo. To further explore the sponge microRNA (miRNA) of PVT1 in HCC, we used TCGA, GEO, a gene microarray, and target prediction algorithms. TCGA and GEO and the gene microarray were used to select the differentially expressed miRNAs, and the different target prediction algorithms were applied to predict the target miRNAs of PVT1.

RESULTS:

We found that PVT1 was markedly overexpressed in HCC tissue than in normal liver tissues based on both RT-qPCR and data from TCGA, and the overexpression of PVT1 was closely related to the gender and race of the patient as well as to higher HCC tumor grades. Also, a meta-analysis of 840 cases from multiple sources (TCGA, GEO and the results of our in-house RT-qPCR) showed that PVT1 gained moderate value in discriminating HCC patients from normal controls, confirming the results of RT-qPCR. Additionally, the upregulation of PVT1 could promote HCC cell proliferation in vitro and vivo. Based on the competing endogenous RNA (ceRNA) theory, the PVT1/miR-424-5p/INCENP axis was finally selected for further research. The in silico prediction revealed that there were complementary sequences between PVT1 and miR-424-5p as well as between miR-424-5p and INCENP. Furthermore, a negative correlation trend was found between miR-424-5p and PVT1 based on RT-qPCR, whereas a positive correlation trend was found between PVT1 and INCENP based on data from TCGA. Also, INCENP small interfering RNA (siRNA) could significantly inhibit cell proliferation and viability.

CONCLUSIONS:

We hypothesized that PVT1 could affect the biological function of HCC cells via targeting miR-424-5p and regulating INCENP. Focusing on the new insight of the PVT1/miR-424-5p/INCENP axis, this study provides a novel perspective for HCC therapeutic strategies.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN Neoplásico / Proteínas Cromosómicas no Histona / Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / ARN Largo no Codificante / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN Neoplásico / Proteínas Cromosómicas no Histona / Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / ARN Largo no Codificante / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: China