Long noncoding RNA ENST00000455974 plays an oncogenic role through up-regulating JAG2 in human DNA mismatch repair-proficient colon cancer

Biochem Biophys Res Commun. 2019 Jan 8;508(2):339-347. doi: 10.1016/j.bbrc.2018.11.088. Epub 2018 Nov 23.

Abstract

DNA mismatch repair-proficient colon cancer is the most common type of colon cancer, but its initiation and progression are still unknown. Our previous study has revealed that a long noncoding RNA (lncRNA) ENST00000455974 was significantly associated with TNM stage and distant metastasis in patients with DNA mismatch repair-proficient (pMMR) colon cancer (CC). Here, firstly, we observed that ENST00000455974 was gradual increased across colon normal-adenoma-carcinoma-metastasis sequence by quantitative real-time PCR. Secondly, ENST00000455974 showed a better sensitivity and specificity than CEA and CA19-9 in the diagnosis of pMMR CC by drawing the receiver operating characteristic (ROC) curve. Thirdly, a higher level of ENST00000455974 was associated with a poorer patient survival. Furthermore, Knockdown of ENST00000455974 led to reduced proliferation and migration of colon cancer cells. Mechanistically, ENST00000455974 was mainly located in the nucleus of colon cancer cells and it promoted the growth and metastasis of pMMR CC cells through up-regulating JAG2.

Keywords: Colon cancer; Migration; Proficient DNA mismatch repair; Proliferation; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / pathology
  • Caco-2 Cells
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • DNA Mismatch Repair / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Jagged-2 Protein / genetics*
  • Jagged-2 Protein / metabolism*
  • Kaplan-Meier Estimate
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Oncogenes
  • Prognosis
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Up-Regulation

Substances

  • JAG2 protein, human
  • Jagged-2 Protein
  • RNA, Long Noncoding