H19 Facilitates Tongue Squamous Cell Carcinoma Migration and Invasion via Sponging miR-let-7

Oncol Res. 2019 Feb 5;27(2):173-182. doi: 10.3727/096504018X15202945197589. Epub 2018 Mar 9.

Abstract

The long noncoding RNA (lncRNA) H19 has been described to participate in the metastasis of various tumors. Nevertheless, whether H19 promotes or impedes tongue squamous cell carcinoma (TSCC) cell migration and invasion remains controversial. Here we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with unmetastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squamous cells. Subsequently, depletion of H19 impaired the migration and invasion abilities of TSCC cells. Mechanistically, we demonstrated that H19 functions as a competing endogenous RNA (ceRNA) to sponge miRNA let-7a, leading to an increase in a let-7a target, the key regulator of tumor metastasis HMGA2, which is enriched in TSCC tissues and cell lines. Intriguingly, inhibition of let-7a significantly rescued the short hairpin H19 (shH19)-induced decrease in TSCC migration and invasion. These findings revealed that the H19/let-7a/HMGA2/EMT axis plays a critical role in the regulation of TSCC migration and invasion, which may provide a new therapeutic target for TSCC.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Female
  • HMGA2 Protein / analysis
  • HMGA2 Protein / physiology
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / physiology*
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Tongue Neoplasms / pathology*

Substances

  • H19 long non-coding RNA
  • HMGA2 Protein
  • HMGA2 protein, human
  • MicroRNAs
  • RNA, Long Noncoding
  • mirnlet7 microRNA, human