@article{TEXTUAL,
      recid = {5478},
      author = {Zhu, Wei and Huang, Meiyuan and Thakur, Abhimanyu and Yan,  Yuanliang and Wu, Xiaoying},
      title = {FGF19 promotes cell autophagy and cisplatin  chemoresistance by activating MAPK signaling in ovarian  cancer},
      journal = {PeerJ},
      address = {2023-02-02},
      number = {TEXTUAL},
      abstract = {&lt;p&gt;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.&lt;/p&gt;  &lt;p&gt;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.&lt;/p&gt;  &lt;p&gt;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-γ, 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.&lt;/p&gt; &lt;p&gt;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.&lt;/p&gt;},
      url = {http://knowledge.uchicago.edu/record/5478},
}