Long non-coding RNA TUSC8 inhibits breast cancer growth and metastasis via miR-190b-5p/MYLIP axis

Aging (Albany NY). 2020 Feb 9;12(3):2974-2991. doi: 10.18632/aging.102791. Epub 2020 Feb 9.

Abstract

The lncRNA tumor suppressor candidate 8 (TUSC8) plays a critical role in the development of several cancers. However, the biological functions and underlying molecular mechanisms of TUSC8 with respect to breast cancer remain largely unclear. Here, we found that TUSC8 was significantly down-regulated in breast cancer tissues and its high expression predicted better prognosis of breast cancer patients. Functionally, knock-down of TUSC8 drastically promoted the proliferation, migration and invasion of breast cancer cells in vitro and facilitated tumorigenicity and metastasis in vivo. Mechanistically, the results of luciferase reporter, RIP and RNA pull-down assays proved that TUSC8 functioned as molecular sponge for miR-190b-5p. Furthermore, we showed that TUSC8 served as a competing endogenous RNA (ceRNA) of myosin regulatory light chain interacting protein (MYLIP) through competitively binding with miR-190b-5p and suppressed breast cancer metastasis through regulating the expression of epithelial-mesenchymal transition (EMT) related markers. Clinically, the receiver operating characteristic curve (ROC) analyses revealed that the combination usage of TUSC8 and MYLIP might become novel promising diagnostic biomarkers for breast cancer. Taken together, these results suggested that TUSC8 inhibited breast cancer growth and metastasis via miR-190b-5p/MYLIP axis, providing us new insights into developing potential therapeutic targets for breast cancer patients.

Keywords: MYLIP; TUSC8; breast cancer; ceRNA; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • Neoplasms, Experimental
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Ubiquitin-Protein Ligases

Substances

  • MIRN190b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUSC8 long non-coding RNA, human
  • MYLIP protein, human
  • Ubiquitin-Protein Ligases