Comprehensive network analysis of dysregulated genes revealed MNX1‐AS1/hsa‐miR‐4697‐3p/HOXB13 axis in ovarian cancer chemotherapy response. Issue 8 (24th June 2022)

• Record Type: Journal Article
• Authors: Wu, Anqi; Liu, Jiaqi; Zhang, Xiaojun; Niu, Chenxi; Shu, Guang; Yin, Gang
• Is Part Of: Cancer science. Volume 113:Issue 8(2022)
• Page Start: 2627
• Page End: 2641
• Publication Date: 2022-06-24
• Subjects: ceRNA -- chemoresistance -- HOXB13 -- miR‐4697‐3p -- MNX1‐AS1 -- ovarian cancer; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15447
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Poor chemotherapy response is the main obstacle of ovarian cancer (OC) treatment. Platinum‐refractory and ‐resistant patients are associated with a worse outcome than platinum‐sensitive and partially sensitive patients, but the comprehensive similarities and differences among them are not yet clear. In this study, we analyzed the data of patients with different chemotherapy response in The Cancer Genome Atlas. We found a minority of altered genes were overlapped in refractory and resistant groups, as did the enriched pathways and Gene Ontology terms. We noticed that the neural signaling and drug metabolism enzymes were more significantly enriched and the protein–protein interaction supported these results. The transcription analysis highlighted PDX1 as the common and central transcription factor in both refractory and resistant groups. The competing endogenous RNA (ceRNA) network shared no common ceRNA pairs, indicating a major difference in noncoding RNA post‐transcriptional regulation. In the end, we validated the expression, regulation, binding, and effect on chemotherapy response for selected MNX1‐AS1/hsa‐miR‐4697‐3p/HOXB13 in OC cell lines. Our study offered a novel and comprehensive insight into chemotherapy response, and potential targets for improving chemotherapy response in OC. Abstract : Our work revealed the chemotherapy response related dysregulated function, transcriptional regulation, and lncRNA based ceRNA regulation landscape in OC, thus offered a novel and comprehensive insight into chemotherapy response. Also, we validated the MNX1‐AS1/ has‐miR‐4697‐3p/ HOXB13 axis could affect carboplatin sensitive for the first time, which could be potential targets for improving chemotherapy response in OC.