Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer

Cancer Lett. 2016 Jun 28;376(1):62-73. doi: 10.1016/j.canlet.2016.03.022. Epub 2016 Mar 21.

Abstract

The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors, and these lncRNAs can be useful as diagnostic indicators and anti-tumor targets. Therefore, it is important to identify lncRNAs that can be used for the clinical prevention and treatment of colorectal cancer (CRC). Here, we report that cancer susceptibility candidate 11 (CASC11) was upregulated in CRC tissues; increased CASC11 expression in CRC was associated with tumor size, serosal invasion, lymph metastasis, and the tumor-node-metastasis (TNM) stage. Functional experiments showed that CASC11 can promote CRC cell proliferation and metastasis in vitro and in vivo. Furthermore, CASC11 can target heterogeneous ribonucleoprotein K (hnRNP-K) to activate WNT/β-catenin signaling in CRC cells. In addition, we found that c-Myc directly bound to the promoter regions of CASC11 and increased promoter histone acetylation to enhance CASC11 expression. Together, our findings indicate that the novel lncRNA CASC11 may serve as a candidate diagnostic biomarker and a promising therapeutic target for CRC.

Keywords: CASC11; Colorectal cancer; hnRNP-K; lncRNA; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • HEK293 Cells
  • HT29 Cells
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism*
  • Heterografts
  • Histones / metabolism
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • Histones
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • beta Catenin
  • long noncoding RNA CASC11, human