Distinct roles of miR-34 family members on suppression of lung squamous cell carcinoma

Dangze Sun, Yao Wu, Shanshan Zhang, Yaxuan Han, Jinglong Shen, Wenhao Zheng, Lin Wei, Yugang Liu, Leipeng Ren, Zhenning Gu, You Liu, Shuhui Liu, Chao Ding

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

miR-34, whose mimic was used on phase I clinical trial, has been extensively reported since its dysfunction in various cancers including non-small-cell lung cancer (NSCLC). However, the roles of miR-34 family members in the progression of lung squamous carcinoma (SCC) in patients who have occupational-exposure experience are unclear yet. Here, we comprehensively investigated the expression levels of miR-34 family members in SCC patients and compared the roles of them in SCC in vitro and vivo. The results showed that the average levels of miR-34a and miR-34b/c were decreased in patients. The analysis of miR-34a to miR-34b/c levels in patients graded different stages or metastases or recurrence showed that miR-34b/c was reduced earlier and more significantly than miR-34a. In vitro assays demonstrated that both miR-34a and miR-34b/c inhibits SCC cells proliferation, migration and invasion via Notch1 pathway, while miR-34b/c effects more than miR-34a does. As miR-34a was significantly decreased in cancer recurrence, the further analysis of relationship between miR-34a and stem cell adhesion molecular CD44 showed that miR-34a was significantly correlated with CD44 levels in patients. Knockdown of CD44 significantly blocked miR-34a mediated inhibition of cell migration and invasion. Treating the purified CD44hi cells with miR-34 overexpression lentivirus inhibited the tumor outgrowth. By contrast, anti-miR-34 facilitated tumor development of CD44low cells. Our study showed that miR-34 family members are negative regulator for SCC development, even though the inhibition is mediated by multiple and complicated signal pathways, which provides theoretical basis for SCC treatment and a biomarker candidate for SCC prognosis.

Original languageEnglish
Article number111967
JournalBiomedicine and Pharmacotherapy
Volume142
DOIs
StatePublished - Oct 2021

Keywords

  • Cell growth
  • Lung squamous cell cancer
  • Metastasis
  • MiR-34a
  • MiR-34b/c

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