Mir-335 restrains the aggressive phenotypes of ovarian cancer cells by inhibiting col11a1

Yi Hui Wu, Yu Fang Huang, Tzu Hao Chang, Pei Ying Wu, Tsung Ying Hsieh, Sheng Yen Hsiao, Soon Cen Huang, Cheng Yang Chou

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPβ/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

Original languageEnglish
Article number6257
JournalCancers
Volume13
Issue number24
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Clinical oncology
  • COL11A1
  • Collagen type XI alpha 1
  • EOC cells
  • Epithelial ovarian carcinoma
  • MiR-335
  • MiR-509
  • MiRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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