LncRNA SNHG12 regulates the miR-101-3p/CUL4B axis to mediate the proliferation, migration and invasion of non-small cell lung cancer

Kaohsiung J Med Sci. 2021 Aug;37(8):664-674. doi: 10.1002/kjm2.12389. Epub 2021 May 17.

Abstract

Mounting evidence has shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and tumor progression. SNHG12 has been identified in multiple types of malignant tumors. However, the role of SNHG12 in human non-small cell lung cancer (NSCLC) is poorly characterized, and the relevant underlying mechanism remains unclear. The expression levels of SNHG12, miR-101-3p, and CUL4B in collected human NSCLC tumor tissues and NSCLC cell lines were tested via qRT-PCR. Then, NSCLC cellular proliferation, migration and invasion were determined, followed by MTT, scratch and Transwell assays. Dual-luciferase reporter assays and RNA pulldown assays were adopted to explore the target site. Moreover, western blotting was performed to detect the relevant protein expression concerning the CUL4B/PI3K/AKT pathway. This study clarified that SNHG12 knockdown significantly reduced proliferation, migration, invasion and EMT of NSCLC cells. Our data indicated that SNHG12 targeted and negatively regulated miR-101-3p, and this depletion reversed the inhibitory effect of si-SNHG12 on NSCLC cells. Furthermore, CUL4B was confirmed as a functional target of miR-101-3p, and its knockdown resulted in a strong alleviation of the NSLCL cell phenotype, which was enhanced by the silencing of miR-101-3p. Mechanistically, we found that SNHG12 regulated miR-101-3p to modulate the PI3K/AKT pathway mediated by CUL4B.These observations suggested that lncRNA SNHG12-mediated miR-101-3p downregulation regulated the malignant phenotype of NSCLC cells by targeting CUL4B through the PI3K/AKT pathway, which may present a path to novel therapeutic strategies for NSCLC therapy.

Keywords: CUL4B; NSCLC; PI3K/AKT; SNHG12; miR-101-3p.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cullin Proteins / metabolism*
  • Epithelial-Mesenchymal Transition
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*

Substances

  • CUL4B protein, human
  • Cullin Proteins
  • MIRN101 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SNHG12 long non-coding RNA, human
  • Proto-Oncogene Proteins c-akt