Long noncoding RNA lung cancer associated transcript 1 promotes proliferation and invasion of clear cell renal cell carcinoma cells by negatively regulating miR-495-3p

J Cell Biochem. 2018 Sep;119(9):7599-7609. doi: 10.1002/jcb.27099. Epub 2018 Jun 22.

Abstract

Recently, long noncoding RNAs have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). Here, we focused on the long noncoding RNA lung cancer associated transcript 1 (LUCAT1) based on clear cell RCC (ccRCC) the cancer genome atlas (TCGA) data. However, whether aberrant expression of LUCAT1 in ccRCC is correlated with malignancy, metastasis or prognosis has not been elucidated. In the current study, we found that the expression of LUCAT1 was upregulated in ccRCC tissues and cancer cell lines. Upregulated LUCAT1 was positively correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, higher smoking frequency, nodal metastasis and shorter overall survival in patients with ccRCC. Inhibition of LUCAT1 by small interfering RNA reduced cell proliferation and invasion of ccRCC cells in vitro. In vivo assay showed that the tumor volume and weight were lower in the group of LUCAT1 inhibition than that in the control group. We then found that LUCAT1 directly bound and inhibited the expression of micoRNA-495-3p (miR-495-3p), which subsequently regulated the expression of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1). Collectively, LUCAT1 was critical for proliferation and invasion of ccRCC cells by regulating miR-495-3p and SATB1. Our findings indicated that LUCAT1 and miR-495-3p may offer potential novel therapeutic targets of treatment of ccRCC.

Keywords: LUCAT1; clear cell renal cell carcinoma (ccRCC); long noncoding RNA (lncRNA); miR-495-3p; special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • Matrix Attachment Region Binding Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasm Transplantation
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / pharmacology
  • Survival Analysis
  • Tumor Burden
  • Up-Regulation*

Substances

  • 3' Untranslated Regions
  • MIRN495 microRNA, human
  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • SATB1 protein, human
  • long non-coding RNA LUCAT1, human