1. Academic Validation
  2. Long Noncoding RNA MALAT1 Contributes to Sorafenib Resistance by Targeting miR-140-5p/Aurora-A Signaling in Hepatocellular Carcinoma

Long Noncoding RNA MALAT1 Contributes to Sorafenib Resistance by Targeting miR-140-5p/Aurora-A Signaling in Hepatocellular Carcinoma

  • Mol Cancer Ther. 2020 May;19(5):1197-1209. doi: 10.1158/1535-7163.MCT-19-0203.
Lei Fan  # 1 Xiang Huang  # 2 Jing Chen 3 Kai Zhang 4 Yan-Hong Gu 2 Jing Sun 5 Shi-Yun Cui 5
Affiliations

Affiliations

  • 1 Department of General Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nangjing, P.R. China.
  • 2 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
  • 3 Department of Respiratory, Zhongda Hospital, Southeast University, Nanjing, P.R. China.
  • 4 Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China. cuishiyun@njmu.edu.cn sunj@njmu.edu.cn.
  • # Contributed equally.
Abstract

Long noncoding RNAs (lncRNA) have been found to play critical roles in tumorigenesis and the development of various cancers, including hepatocellular carcinoma (HCC). Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) has been identified as an oncogene and prognostic biomarker in HCC. Here, we demonstrated that MALAT1 expression was obviously high in sorafenib-resistant HCC cells. Furthermore, knockdown of MALAT1 increased sorafenib sensitivity in nonresponsive HCC cells, whereas forced expression of MALAT1 conferred sorafenib resistance to responsive HCC cells in vitro In addition, loss/gain-of-function assays revealed that MALAT1 promoted cell proliferation, migration, and epithelial-mesenchymal transition in HCC cells. Mechanistically, MALAT1 regulated Aurora-A expression by sponging miR-140-5p, thus promoting sorafenib resistance in HCC cells. Moreover, MALAT1 inhibition enhanced the antitumor efficacy of sorafenib in vivo Clinically, we found that MALAT1 expression was negatively correlated with miR-140-5p expression but positively correlated with Aurora-A expression in patients with HCC and that upregulated MALAT1 was closely correlated with poor survival outcomes in patients with HCC. These findings indicated that MALAT1 may be a novel target for prognosis prediction and therapeutic strategies in patients with HCC treated with sorafenib.

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