LncRNA MALAT1 expression inhibition suppresses tongue squamous cell carcinoma proliferation, migration and invasion by inactivating PI3K/Akt pathway and downregulating MMP-9 expression

Eur Rev Med Pharmacol Sci. 2019 Jan;23(1):198-206. doi: 10.26355/eurrev_201901_16765.

Abstract

Objective: LncRNA MALAT1 has been proved to be involved in the development of various types of human cancers while the involvement of MALAT1 in tongue squamous cell carcinoma has not been reported. In view of this, our study aimed to investigate the functionality of MALAT1 in tongue squamous cell carcinoma.

Patients and methods: The expression of MALAT1 in tumor tissues and adjacent healthy tissues of tongue cancer patients, and the serum from tongue cancer patients as well as healthy controls, were detected by quantitative Real Time-PCR (qRT-PCR). ROC curve analysis was performed to analyze the diagnostic value of plasma MALAT1 for tongue cancer. Survival curves were plotted using the Kaplan-Meier method to evaluate the prognostic value of plasma MALAT1 for tongue cancer. CCK-8 assay, transwell migration and invasion assay were performed to investigate the effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells, respectively. The effects of MALAT1 overexpression on the PI3K/Akt pathway and MMP-9 expression were detected by Western blot.

Results: The expression level of MALAT1 was remarkably higher in tumor tissues than that in adjacent healthy tissues. Serum MALAT1 was significantly higher in tongue cancer patients than in healthy controls. MALAT1 knockdown markedly inhibits the proliferation, migration and invasion of tongue cancer cells. MALAT1 knockdown also reduced the phosphorylation level of Akt as well as the expression level of MMP-9. It showed no significant effects on Akt expression, while PI3K activator treatment reduced the inhibitory effects of MALAT1 knockdown on the proliferation, migration and invasion of tongue cancer cells.

Conclusions: LncRNA MALAT1 expression inhibition can inhibit the proliferation, migration and invasion of tongue cancer cells by inactivating the PI3K/Akt pathway and downregulating MMP-9. MALAT1 may serve as a target for the treatment of tongue squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Matrix Metalloproteinase 9 / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / genetics
  • Squamous Cell Carcinoma of Head and Neck / blood
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tongue / pathology
  • Tongue Neoplasms / blood
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / mortality
  • Tongue Neoplasms / pathology
  • Young Adult

Substances

  • MALAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • MMP9 protein, human
  • Matrix Metalloproteinase 9