Infection Department, The First Hospital of Lanzhou University, Lanzhou, China.
Department of Ultrasound, The First Hospital of Lanzhou University, Lanzhou, China.
Yonsei Med J. 2019 Aug;60(8):727-734. doi: 10.3349/ymj.2019.60.8.727.
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.
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.
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.
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.
肝细胞癌（HCC）是一种常见的癌症。已报道转移相关肺腺癌转录物 1（MALAT1），一种长链非编码 RNA（lncRNA），在低氧癌细胞中异常表达。MALAT1 在许多恶性肿瘤中发挥重要作用，包括 HCC。本研究旨在探讨 MALAT1 在低氧 HCC 细胞中的作用及其潜在的调节机制。
采用定量逆转录 PCR（qRT-PCR）检测 HCC 细胞中 MALAT1 和 microRNA-200a（miR-200a）的 mRNA 水平。采用 Transwell 检测细胞侵袭和迁移能力。Starbase v2.0 和荧光素酶报告基因检测用于鉴定 MALAT1 和 miR-200a 之间的关联。MTT 法和流式细胞术分别用于检测细胞增殖和凋亡。
MALAT1 在低氧 HCC 细胞中表达明显上调。低氧促进 Hep3B 细胞增殖、迁移和侵袭，并抑制细胞凋亡，而 MALAT1 敲低则减弱了这些作用。Starbase v2.0 显示 MALAT1 和 miR-200a 具有互补区域，荧光素酶报告基因检测证实 MALAT1 在 Hep3B 细胞中与 miR-200a 相互作用。此外，MALAT1 负调控 miR-200a 的表达。低氧 HCC 细胞中 miR-200a 水平明显下调。上调 miR-200a 抑制 Hep3B 细胞在低氧条件下的增殖、迁移和侵袭，并诱导细胞凋亡。有趣的是，下调 miR-200a 部分逆转了 MALAT1 敲低对 Hep3B 细胞在低氧条件下的肿瘤抑制作用。
lncRNA MALAT1 通过与低氧 Hep3B 细胞中的 miR-200a 相互作用参与增殖、迁移、侵袭和凋亡，揭示了 MALAT1 参与低氧 HCC 进展的新机制。
