Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a

Abstract

Purpose Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. Materials and Methods Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and 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 that MALAT1 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 downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of 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 in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.

<p>LncRNA MALAT1 Regulates the Progression and Cisplatin Resistance of Ovarian Cancer Cells via Modulating miR-1271-5p/E2F5 Axis</p>

“…25 Miao et al reported that lncRNA ANRIL changed the sensitivity of OC cells to DDP by mediating let-7a and HMGA2 levels. 26 LncRNA linc00312 regulated DDP resistance of OC cells via modulating Bcl-2/Caspase-3 pathway. 27 Therefore, lncRNAs exerted the crucial function in DDP-resistant OC cells.…”

<p>Regulatory Networks of LncRNA MALAT-1 in Cancer</p>

“…29 Hypoxia, which plays an important role in solid tumor development, can enhance MALAT-1 expression in HCC. 24,30 MALAT-1 was shown to modulate the proliferation, apoptosis, migration, and invasion HCC cells exposed to hypoxia by sponging miR-200a. 24 MALAT-1 indirectly activates Sirt1 deacetylase by competing for binding with Depleted in breast cancer (DBC)1; this ultimately results in the deacetylation of p53, which inhibits proapoptosis gene expression and promotes tumor cell growth.…”

MicroRNA gga-miR-200a-3p modulates immune response via MAPK signaling pathway in chicken afflicted with necrotic enteritis

“…Several functional studies on miR-200a have been conducted in vertebrates. In human and mice, it was reported that MALAT1 affected proliferation, migration, invasion, and apoptosis during the progression of hypoxic hepatocellular carcinoma by sponging miR-200a [11]. Moreover, miR-200a mediated the proliferation of hepatic stellate cells and development of fibrosis by targeting the 3′-UTR of SIRT1 via the SIRT1/Notch signal pathway [12].…”