Downregulation of LncRNA-RP11-317J10.2 promotes cell proliferation and invasion and predicts poor prognosis in colorectal cancer

Scand J Gastroenterol. 2018 Jan;53(1):38-45. doi: 10.1080/00365521.2017.1392597. Epub 2017 Oct 26.

Abstract

Objectives: Using microarray analysis, we previously showed that many lncRNAs are differentially expressed in colorectal cancer (CRC) tissues compared with normal tissues, suggesting that lncRNAs may be involved the initiation and progression of CRC. In this study, we investigated the expression and function of lncRNA-RP11-317J10.2 in human CRC tissues and cell lines.

Methods: LncRNA-RP11-317J10.2 expression level was analyzed in 52 colon cancer and cell lines. We used shRNA to knock-down the expression of RP11-317J10.2, and then proliferation assay, colony formation assay, Boyden chamber assay, FACS and Kaplan-Meier survival analysis were performed to explore the biological effect of RP11-317J10.2. Cyclin D1 protein level was detected by Western blot.

Results: LncRNA-RP11-317J10.2 is downregulated in CRC and decreased expression is significantly associated with advanced tumor stage, larger tumor size and poor prognosis. RNA interference-mediated knockdown of lncRNA-RP11-317J10.2 in CRC cells promotes G1-to-S cell cycle transition, enhances invasiveness and facilitates cell growth in vitro and in mouse tumor xenograft models. Cyclin D1 was upregulated by lncRNA-RP11-317J10.2 knockdown, and co-expression of cyclin D1-targeting siRNA abrogates the pro-tumorigenic effects of lncRNA-RP11-317J10.2 knockdown.

Conclusions: This study reveals a crucial role for lncRNA-RP11-317J10.2 in CRC growth and invasion via upregulation of cyclin D1 expression and suggests that expression of this lncRNA may be a potential prognostic biomarker for CRC.

Keywords: Colorectal cancer; cell invasion; cell proliferation; long non-coding RNA; prognosis.

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • Up-Regulation

Substances

  • CCND1 protein, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Cyclin D1