MicroRNA let-7a inhibits the proliferation and invasion of nonsmall cell lung cancer cell line 95D by regulating K-Ras and HMGA2 gene expression

Cancer Biother Radiopharm. 2013 Mar;28(2):131-7. doi: 10.1089/cbr.2012.1307. Epub 2012 Nov 7.

Abstract

MicroRNAs are closely linked to tumor metastasis and let-7a may play a role in inhibiting the proliferation, invasion, and metastasis of lung cancer. In vitro, we aim to observe the impact of let-7a on the proliferation and invasion of the nonsmall cell lung cancer cell line 95D by constructing a lentiviral vector that expresses let-7a. Cell proliferation assays and Transwell experiments were used to compare the proliferation and invasion of the 95D cell group with let-7a overexpressed or inhibited. Real-time polymerase chain reaction and immunoblotting analysis were used to compare the expression of K-RAS and HMGA2 at mRNA and the protein level in the above groups. The results showed the cells in the let-7a overexpressed group were significantly less proliferative and invasive than those in the let-7a inhibited group (p < 0.05). K-RAS and HMGA2 mRNA levels were significantly higher in the let-7a overexpressed group than those in the let-7a inhibited group (p < 0.05). However, the protein levels of K-RAS and HMGA2 were significantly lower in the let-7a overexpressed group than those in the let-7a inhibited group (p < 0.05). We suppose that let-7a inhibits the proliferation and invasion of the cell line 95D by regulating the translation of K-RAS and HMGA2 mRNA, not the transcription of the mRNA itself.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Adhesion
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • HMGA2 Protein / genetics*
  • HMGA2 Protein / metabolism
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • ras Proteins / genetics*
  • ras Proteins / metabolism

Substances

  • HMGA2 Protein
  • KRAS protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • mirnlet7 microRNA, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins