MALAT1 Promotes Tumorigenesis and Increases Cellular Sensitivity to Herceptin in HER2-positive Breast Cancer

Curr Cancer Drug Targets. 2021;21(10):860-869. doi: 10.2174/1568009621666210618164300.

Abstract

Background: The function of MALAT1, a long non-coding RNAs (lncRNA), in HER2- positive breast cancer remains largely unexplored.

Objectives: This study aimed to investigate the effect of MALAT1 on tumor development in HER2-positive breast cancer.

Methods: We detected MALAT1 expression in HER2-positive breast cancer cells and tissues, and analyzed the effects of MALAT1 on cell proliferation in HER2-positive breast cancer cells lines (BT-474 and SKBR3). A mouse xenograft model was established for detecting the function of MALAT1 in HER2-positive breast cancer.

Results and discussion: As a result, MALAT1 was remarkably up-regulated in HER2-positive breast cancer both in cells and tissues. In addition, the silencing of MALAT1 inhibited the proliferation of HER2-positive breast cancer cells both in vitro and in vivo. Furthermore, knockdown of MALAT1 by shRNA down-regulated DNMT1, DNMT3a, and DNMT3b, while up-regulated BRCA1 and PTEN in HER2-positive breast cancer both in cell lines and mouse xenograft models.

Conclusion: In short, MALAT1 might be a potential biomarker and therapeutic target for HER2- positive breast cancer therapy.

Keywords: DNMTs; HER2-positive breast cancer; MALAT1; herceptin resistance.; long non-coding RNA; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs*
  • RNA, Long Noncoding* / genetics
  • Trastuzumab / pharmacology

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Trastuzumab