Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a
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Purpose: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 playsa significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCCcells and its underlying regulatory mechanism. Materials and Methods: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels ofMALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbasev2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferationand apoptosis were measured by MTT assay and flow cytometry, respectively. Results: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration,and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed thatMALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulatedin HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and inducedapoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effectof knockdown of MALAT1 on Hep3B cells in hypoxic condition. Conclusion: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a inhypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.
Abstract
Purpose: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 playsa significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCCcells and its underlying regulatory mechanism. Materials and Methods: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels ofMALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbasev2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferationand apoptosis were measured by MTT assay and flow cytometry, respectively. Results: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration,and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed thatMALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulatedin HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and inducedapoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effectof knockdown of MALAT1 on Hep3B cells in hypoxic condition. Conclusion: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a inhypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.
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