miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway

Autophagy, characterized by the elevator of autophagy-related gene 14 (ATG14) and the dysregulation of autophagy-related proteins, contributes to the cisplatin (DDP) resistance in ovarian cancer. Forkhead box protein P1 (FOXP1), which is a well-defined transcription factor, is reported to have the o...

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Vydáno v:Cell cycle (Georgetown, Tex.) Ročník 19; číslo 2; s. 193 - 206
Hlavní autoři: Hu, Zhenhua, Cai, Mingbo, Zhang, Ying, Tao, Lingling, Guo, Ruixia
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Taylor & Francis 17.01.2020
Témata:
Adaptor Proteins, Vesicular Transport - metabolism
Animals
ATG14
autophagy
Autophagy - drug effects
Autophagy - genetics
Autophagy-Related Proteins - metabolism
Base Sequence
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - genetics
Cisplatin - pharmacology
Down-Regulation - drug effects
Down-Regulation - genetics
Drug Resistance, Neoplasm - drug effects
Drug Resistance, Neoplasm - genetics
Female
Forkhead Transcription Factors - metabolism
FOXP1
Gene Expression Regulation, Neoplastic - drug effects
Humans
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
miR-29c-3p
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
Repressor Proteins - metabolism
Research Paper
Signal Transduction - drug effects
autophagy
ATG14
miR-29c-3p
FOXP1
Ovarian cancer
ISSN:1538-4101, 1551-4005, 1551-4005
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Shrnutí:Autophagy, characterized by the elevator of autophagy-related gene 14 (ATG14) and the dysregulation of autophagy-related proteins, contributes to the cisplatin (DDP) resistance in ovarian cancer. Forkhead box protein P1 (FOXP1), which is a well-defined transcription factor, is reported to have the oncogenic effect on ovarian cancer. This study aims to identify the effect of miR-29c-3p/FOXP1/ATG14 pathway in regulating autophagy and DDP resistance in ovarian cancer. The expressions of miR-29c-3p, FOXP1, ATG14 and autophagy-related proteins were detected in DDP-sensitive ovarian cancer cell lines (SKOV3 and A2780) and DDP-resistant cell lines (SKOV3/DDP and A2780/DDP). Cell viability was detected using the MTT assay. The therapeutic effect of miR-29c-3p overexpression was observed in the xenograft model of nude mice.Compared with DDP-sensitive cells, miR-29c-3p was decreased in DDP-resistant cells, and an enhancement of FOXP1, ATG14, autophagy, and drug resistance was shown in DDP-resistant cells. The anti-resistant effect of miR-29c-3p was observed as overexpressing miR-29c-3p inhibited cell viability of DDP-resistant cells. Moreover, FOXP1 was a target of miR-29c-3p, which was confirmed by the luciferase reporter assay, and ATG14 was transactivated by FOXP1, which was confirmed by the ChIP assay. Overexpression of miR-29c-3p increased DDP sensitivity by downregulating FOXP1/ATG14 in vitro. The tumor volume was reduced after the injection of miR-29c-3p-overexpressing SKOV3/DDP cells in vivo. Overexpression of miR-29c-3p inhibited autophagy and DDP resistance partly via downregulating FOXP1/ATG14 pathway, suggesting miR-29c-3p as a novel target in overcoming DDP resistance in ovarian cancer.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1538-4101
1551-4005
1551-4005
DOI:10.1080/15384101.2019.1704537