Let-7a inhibits tumor cell growth and metastasis by directly targeting RTKN in human colon cancer

Biochem Biophys Res Commun. 2016 Sep 16;478(2):739-45. doi: 10.1016/j.bbrc.2016.08.018. Epub 2016 Aug 4.

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity. MicroRNAs (miRNAs) are endogenous small RNAs that play important roles in regulating multiple biological and pathologic processes. The differential expression of miRNAs in CRC was first reported in 2003. Accumulated evidence indicates that lethal-7a (let-7a, miRNA) generally functions as a tumor suppressor in several human cancers. However, the role of let-7a in human colon cancer remains unclear. The aim of this study was to investigate the biological functions of let-7a and its potential role in colon cancer. We first discovered that let-7a level was significantly decreased in colon cancer tissues and cell lines (HT-29, HCT-116, LoVo, SW480, and SW620). To explore the effects of let-7a on colon cancer, let-7a over-expressed HCT-116 and SW620 cells were constructed. Further studies demonstrated that over-expressed let-7a could remarkably inhibit HCT-116 and SW620 cell growth and metastasis by directly down-regulating Rhotekin (RTKN). When RTKN was reintroduced into let-7a mimic transfected HCT-116 or SW620 cells, the inhibition effects of let-7a on colon cancer cell growth and metastasis were markedly reversed. In conclusion, our research shows that let-7a can inhibit tumor cell growth and metastasis by directly targeting RTKN in human colon cancer.

Keywords: Colon cancer; EMT; Let-7a; Metastasis; RTKN.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Binding Sites
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • GTP-Binding Proteins
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Metastasis
  • Oligoribonucleotides, Antisense / genetics
  • Oligoribonucleotides, Antisense / metabolism
  • Signal Transduction

Substances

  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • MicroRNAs
  • Oligoribonucleotides, Antisense
  • RTKN protein, human
  • mirnlet7 microRNA, human
  • GTP-Binding Proteins