The long noncoding RNA TPTE2P1 promotes the viability of colorectal cancer cells

J Cell Biochem. 2019 Apr;120(4):5268-5276. doi: 10.1002/jcb.27801. Epub 2018 Nov 1.

Abstract

Long noncoding RNAs (lncRNAs) have important functions in tumor development and progression, including colorectal cancer (CRC), but their roles are not completely understood. In this study, the roles of the lncRNA transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1), previously implicated in gallbladder cancer cell migration and invasion, were evaluated in CRC. In particular, quantitative polymerase chain reaction was used to quantify TPTE2P1 levels in tumor tissues and cell lines. The association between TPTE2P1 and survival was analyzed using the online tool OncoLnc. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, colony formation assays, and flow cytometry were used to evaluate the effects of TPTE2P1 on viability, cell cycle progression, and apoptosis. Signaling pathway proteins were quantitated by Western blot analysis. Finally, the role of TPTE2P1 was analyzed in vivo using mouse models. TPTE2P1 levels were significantly higher in CRC tissues than in adjacent normal tissues. Higher expression was associated with a poor survival rate. The silencing of TPTE2P1 led to cell cycle arrest at the S phase and thereby inhibited cell viability. TPTE2P1 knockdown also caused cancer cell apoptosis via the activation of the apoptosis regulator (BCL2)/caspase 3 signaling cascade. In addition, the inhibition of TPTE2P1 had suppressive effects on tumors in vivo. TPTE2P1 is upregulated in CRC and plays essential roles in the regulation of cell viability in vitro and tumor formation in vivo.

Keywords: Bcl-2; apoptosis; caspase 3; colorectal cancer (CRC); transmembrane phosphoinositide 3-phosphatase and tensin homolog 2 pseudogene 1 (TPTE2P1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Mice
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics

Substances

  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Long Noncoding
  • Caspase 3