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

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
文章編號6257
期刊Cancers
13
發行號24
DOIs
出版狀態已發佈 - 12月 2021

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

指紋

深入研究「Mir-335 restrains the aggressive phenotypes of ovarian cancer cells by inhibiting col11a1」主題。共同形成了獨特的指紋。

引用此