Dataset Information

The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3'UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2.

ABSTRACT: High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically, RNA immunoprecipitation assays showed that the microprocessor Drosha or DGCR8 interacted with HMGA2 mRNA in hepatoma cells. Then, Dicer contributes to the generation of the fragment HMGA2-sh-3p20 from the HMGA2-sh. HMGA2-sh-3p20 was screened by PCR analysis. Interestingly, HMGA2-sh-3p20 increased the expression of HMGA2 through antagonizing the tristetraprolin (TTP)-mediated degradation of HMGA2. HMGA2-sh-3p20 inhibited the expression of PTEN by targeting the 3'UTR of PTEN mRNA. In addition, the overexpression of PTEN could downregulate HMGA2 expression. Significantly, we documented the ability of HMGA2-sh-3p20 to promote the growth of hepatoma cells in vitro and in vivo. Thus, we conclude that the fragment HMGA2-sh-3p20 from HMGA2 mRNA 3'UTR promotes the growth of hepatoma cells by upregulating HMGA2. Our finding provides new insights into the mechanism by which HMGA2 enhances hepatocarcinogenesis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5437003 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3'UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2.

Wang Yuan Y Chen Fuquan F Yang Zhe Z Zhao Man M Zhang Shuqin S Gao Yuen Y Feng Jinyan J Yang Guang G Zhang Weiying W Ye Lihong L Zhang Xiaodong X

Scientific reports 20170518 1

High mobility group A2 (HMGA2) plays a crucial role in the development of cancer. However, the mechanism by which HMGA2 promotes the growth of hepatocellular carcinoma (HCC) remains unclear. Here, we explore the hypothesis that HMGA2 may enhance the growth of hepatoma cells through a fragment based on the secondary structure of HMGA2 mRNA 3'-untranslated region (3'UTR). Bioinformatics analysis showed that HMGA2 mRNA displayed a hairpin structure within its 3'UTR, termed HMGA2-sh. Mechanistically ...[more]

PMID: 28522832

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Project description:Although the functions of long noncoding RNA (lncRNA) called FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) have been well studied in multiple human cancer types, its expression status and detailed roles in cervical cancer remain unknown and merit investigation. This study was aimed at assessing FOXD2-AS1 expression in cervical cancer and at determining its effects on the aggressive behavior of cervical cancer in vitro and in vivo. Expression of FOXD2-AS1 in cervical cancer tissues and cell lines was determined via reverse-transcription quantitative PCR. The effects of FOXD2-AS1 on cervical cancer cells were examined by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow-cytometric analysis, migration and invasion assays, and an in vivo tumorigenicity assay. FOXD2-AS1 was found to be significantly upregulated in cervical cancer tissues and cell lines. High FOXD2-AS1 expression was notably linked with the Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and depth of cervical invasion in patients with cervical cancer. Kaplan-Meier survival analysis revealed significantly shorter overall survival of patients when the tumor expression of FOXD2-AS1 was higher in comparison with those in patients with lower FOXD2-AS1 expression. In vitro functional assays revealed that downregulation of FOXD2-AS1 led to suppression of proliferation, migration, and invasiveness as well as to the induction of apoptosis of cervical cancer cells. In addition, FOXD2-AS1 silencing hindered tumor growth in vivo. Mechanism investigation revealed that FOXD2-AS1 functioned as a molecular sponge of microRNA-760 (miR-760). Furthermore, hepatoma-derived growth factor (HDGF) was validated as a direct target gene of miR-760 in cervical cancer cells. Moreover, an miR-760 knockdown reversed the effects of FOXD2-AS1 silencing on cervical cancer cells. FOXD2-AS1 possesses significant oncogenic activity in cervical cancer progression; this activity is mediated by sponging of miR-760 with consequent upregulation of HDGF. The FOXD2-AS1-miR-760-HDGF axis might harbor promising targets for novel treatment strategies of cervical cancer.

Dataset Information

The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3'UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2.

Publications

The Fragment HMGA2-sh-3p20 from HMGA2 mRNA 3'UTR Promotes the Growth of Hepatoma Cells by Upregulating HMGA2.

Similar Datasets

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