Linc00659, a long noncoding RNA, acts as novel oncogene in regulating cancer cell growth in colorectal cancer

Mol Cancer. 2018 Mar 10;17(1):72. doi: 10.1186/s12943-018-0821-1.

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers and causes of cancer-related death worldwide. In patients with CRC, metastasis is a crucial problem that leads to treatment failure and is the primary cause of the lethality of colon cancer. Long noncoding RNAs (lncRNAs) have recently emerged as critical molecules in the development, cell growth, apoptosis, and metastasis of CRC.

Method: We investigated the transcriptome profiles of human lncRNAs in the primary tumor tissues and in the corresponding normal mucosa of two patients with CRC by using a microarray approach. The expression levels of lncRNAs were verified in colon cancer by real-time PCR. Using bioinformatics approach to illustrate putative biological function of Linc00659 in colon cancer. The effects of Linc00659 on cell growth, proliferation, cell cycle and apoptosis were studies by in vitro assays.

Results: Our data revealed that compared with adjacent normal tissues, 201 lncRNAs were deregulated (fold change ≥ 4 or ≤ 0.25) in CRC tissues. Among them, the expression levels of Linc00659 were significantly increased in colon cancer, and high expression levels were correlated with poor survival in patients with CRC. Bioinformatics analysis results indicated that Linc00659 was significantly coexpressed with cycle-related genes in CRC. Linc00659 expression knockdown could significantly suppress colon cancer cell growth by impairing cell cycle progression. In addition, our results showed that Linc00659 expression knockdown could accelerate cell apoptosis in colon cancer cells treated with chemotherapy drugs. Meanwhile, our results also demonstrated that silencing of Linc00659 expression leads to cell growth inhibition and induced apoptosis, possibly by suppressing PI3K-AKT signaling in colon cancer.

Conclusion: Linc00659 is a novel oncogenic lncRNA involved in colon cancer cell growth by modulating the cell cycle. Our findings give an insight into lncRNA regulation and provide an application for colon cancer therapy.

Keywords: Colorectal carcinoma; Noncoding RNA; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Models, Biological
  • Oncogenes*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Signal Transduction
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt