PMID- 36751636
OWN - NLM
STAT- MEDLINE
DCOM- 20230209
LR  - 20230428
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 11
DP  - 2023
TI  - FGF19 promotes cell autophagy and cisplatin chemoresistance by activating MAPK 
      signaling in ovarian cancer.
PG  - e14827
LID - 10.7717/peerj.14827 [doi]
LID - e14827
AB  - BACKGROUND: Chemotherapy is one of the primary treatments for ovarian cancer 
      patients. Autophagy has been linked to chemotherapy resistance in tumor cells. 
      Recent studies have suggested that fibroblast growth factor 19 (FGF19) may be 
      involved in the onset and progression of malignancies. However, the relationship 
      between FGF19 and autophagy in ovarian cancer is still unknown. METHODS: 
      Next-generation sequencing (NGS) was conducted to analyze gene mutation profiles 
      of 62 cases of high grade serous ovarian cancer (HGSOC). Fluorescence in situ 
      hybridization (FISH) was performed to validate the amplification of FGF19 in 
      HGSOC tissues. Quantitative PCR (qPCR) and immunohistochemistry (IHC) were used 
      to analyze the difference of FGF19 in mRNA and protein expression. Meanwhile, 
      bioinformatics techniques were used to analyze the expression profiles of FGF19 
      and the correlation with prognosis. Besides, immunofluorescence, transmission 
      electron microscopy and Cell Counting Kit 8 (CCK-8) were used to investigate the 
      potential mechanisms. RESULTS: In this study, we found that FGF19 promotes 
      cisplatin resistance in ovarian cancer cells by inducing autophagy. NGS analysis 
      of 62 HGSOC cases identified a significantly amplified gene, FGF19. In addition, 
      the expression level of FGF19 in ovarian cancer samples was higher than that in 
      normal samples. FISH results showed a positive correlation between amplification 
      and expression of FGF19. Knockdown of FGF19 inhibited the cell autophagy through 
      decrease in the expression of LC3 and Beclin 1, and increase in the expression of 
      SQSTM1/p62. Furthermore, we observed that p38 MAPK phosphorylation was 
      down-regulated after FGF19 knockdown. IFN-gamma, a potential p38 MAPK activator, 
      counteracted the inhibition of cell autophagy and the anti-proliferation effect 
      of cisplatin induced by FGF19 knockdown in ovarian cancer cells. CONCLUSION: 
      FGF19 increases autophagy and chemoresistance in ovarian cancer by activating the 
      p38 MAPK pathway. These results could point to FGF19 being a potential 
      therapeutic target for ovarian cancer.
CI  - (c) 2023 Zhu et al.
FAU - Zhu, Wei
AU  - Zhu W
AD  - Department of Pathology, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - Department of Pathology, School of Basic Medical Science, Central South 
      University, Changsha, China.
FAU - Huang, Meiyuan
AU  - Huang M
AD  - Department of Pathology, Zhuzhou Hospital Affiliated to Xiangya School of 
      Medicine, Central South University, Zhuzhou, China.
FAU - Thakur, Abhimanyu
AU  - Thakur A
AD  - Pritzker School of Molecular Engineering, Ben May Department for Cancer Research, 
      University of Chicago, Chicago, Illinois, USA.
FAU - Yan, Yuanliang
AU  - Yan Y
AUID- ORCID: 0000-0001-6610-3617
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 
      Central South University, Changsha, China.
FAU - Wu, Xiaoying
AU  - Wu X
AD  - Department of Pathology, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - Department of Pathology, School of Basic Medical Science, Central South 
      University, Changsha, China.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 
      Central South University, Changsha, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230202
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (FGF19 protein, human)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Humans
MH  - Female
MH  - Cisplatin
MH  - *Antineoplastic Agents/pharmacology
MH  - Drug Resistance, Neoplasm
MH  - In Situ Hybridization, Fluorescence
MH  - Cell Line, Tumor
MH  - *Ovarian Neoplasms/drug therapy
MH  - Autophagy
MH  - Fibroblast Growth Factors/genetics
PMC - PMC9899438
OTO - NOTNLM
OT  - Autophagy
OT  - Chemoresistance
OT  - FGF19
OT  - MAPK
OT  - Ovarian cancer
COIS- Yuanliang Yan is an Academic Editor for PeerJ.
EDAT- 2023/02/09 06:00
MHDA- 2023/02/10 06:00
PMCR- 2023/02/02
CRDT- 2023/02/08 01:59
PHST- 2022/10/13 00:00 [received]
PHST- 2023/01/09 00:00 [accepted]
PHST- 2023/02/08 01:59 [entrez]
PHST- 2023/02/09 06:00 [pubmed]
PHST- 2023/02/10 06:00 [medline]
PHST- 2023/02/02 00:00 [pmc-release]
AID - 14827 [pii]
AID - 10.7717/peerj.14827 [doi]
PST - epublish
SO  - PeerJ. 2023 Feb 2;11:e14827. doi: 10.7717/peerj.14827. eCollection 2023.