miR-335 Restrains the Aggressive Phenotypes of Ovarian Cancer Cells by Inhibiting COL11A1
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Cancers - 13(2021), 24 vom: 13. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yi-Hui [VerfasserIn] |
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| Links: |
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| Themen: |
COL11A1 |
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| Anmerkungen: |
Date Revised 29.12.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers13246257 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM334807816 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COL11A1 | |
| 650 | 4 | |a EOC cells | |
| 650 | 4 | |a clinical oncology | |
| 650 | 4 | |a collagen type XI alpha 1 | |
| 650 | 4 | |a epithelial ovarian carcinoma | |
| 650 | 4 | |a miR-335 | |
| 650 | 4 | |a miR-509 | |
| 650 | 4 | |a miRNA | |
| 700 | 1 | |a Huang, Yu-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Tzu-Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Pei-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Tsung-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Hsiao, Sheng-Yen |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Soon-Cen |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Cheng-Yang |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/cancers13246257 |3 Volltext |
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