KH-type splicing regulatory protein (KHSRP) contributes to tumorigenesis by promoting miR-26a maturation in small cell lung cancer

Mol Cell Biochem. 2016 Nov;422(1-2):61-74. doi: 10.1007/s11010-016-2806-y. Epub 2016 Sep 19.

Abstract

KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein that has a role in tumorigenesis of small cell lung cancer. The KHSRP protein level was shown to be significantly increased in small cell lung cancer (SCLC) tumor tissues compared with normal lung tissues by immunohistochemical staining. Moreover, KHSRP protein levels were strongly associated with T stage in patients with SCLC. Using in vitro assays, we found that knockdown of the KHSRP gene inhibited cell proliferation and increased cell apoptosis but had no effect on cell migration and invasion. We also showed that down-regulation of the KHSRP gene suppressed tumor growth in vivo. Further analyses indicated that KHSRP was involved in miR-26a maturation and inhibited the expression of PTEN in SCLC cells. Taken together, these findings suggested that KHSRP plays an important role in SCLC tumorigenesis and could be a potential novel therapeutic target for SCLC treatment.

Keywords: KH-type splicing regulatory protein (KHSRP); Phosphatase and tensin homolog deleted on chromosome ten (PTEN); Small cell lung cancer (SCLC); Tumorigenesis; mir-26a.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / pathology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • KHSRP protein, human
  • MIRN26A microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • Trans-Activators