en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">High-intensity focused ultrasound (HIFU) represents a therapeutic medical procedure that operates by inducing ablation and mechanical disruption. Despite its established efficacy, its potential impact on tumor chemotherapy remains uncertain. Long noncoding RNA (lncRNA) MAFA-AS1 facilitated cancer cell proliferation and fostering drug resistance, but the precise significance and functional implications of MAFA-AS1 in the context of ovarian cancer (OC) remain largely unexplored. The objective of this experiment is to further investigate the potential of HIFU in inhibiting the chemotherapy resistance mechanism of OC. </span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-GB">Materials and Methods:</span></span></span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB"> Five types of human ovarian cancer cells were employed in this study. There were four different groups, namely MAFA-AS1 siRNA, si-NC, pcDNA3.1-HIF-1 (hypoxia-inducible factor-1), and pcDNA3.1-control. Quantitative real-time PCR, cell proliferation assay, apoptosis assay, western blot assay, subcellular fractionation, aerobic glycolysis analysis, RNA immunoprecipitation (RIP), and luciferase reporter assay were conducted for experimentation and validation. </span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-GB">Results: </span></span></span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">Significant upregulation of MAFA-AS1 in OC cells was observed. Through loss-of-function experiments based on HIFU, we unraveled its oncogenic functions in OC. MAFA-AS1 was discovered to bind to HIF-1 mRNA, thereby enhancing its expressed stability. Further investigations revealed an interaction between MAFA-AS1 and fat mass and obesity-associated protein (FTO), positively modulating HIF-1 mRNA stability in an FTO-dependent manner. Importantly, MAFA-AS1 exerts its effects on OC by acting through HIF-1. </span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-GB">Conclusion: </span></span></span></span></span></span><span lang="en-GB" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-GB">The study underscores the role of MAFA-AS1 in promoting aerobic glycolysis and chemical resistance in OC by up-regulating HIF-1 expression, suggesting that targeting MAFA-AS1 holds promise as a therapeutic strategy for OC patients undergoing chemotherapy.</span></span></span></span></span></span></span></span></span></span></div> High-intensity focused ultrasound, lncRNA MAFA-AS1, HIF-1 mRNA stability, m6A modification, chemoresistance, ovarian cancer. 201 210 http://ijrr.com/browse.php?a_code=A-10-1-1312&slc_lang=en&sid=1 M. Huang 7900319475328460029749 7900319475328460029749 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China Y. Peng sypyx14@163.com 7900319475328460029750 7900319475328460029750 Yes Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China Y. Sun 7900319475328460029751 7900319475328460029751 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China W. Gao 7900319475328460029752 7900319475328460029752 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China J. Fei 7900319475328460029753 7900319475328460029753 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China C. Zhou 7900319475328460029754 7900319475328460029754 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China L. Xie 7900319475328460029755 7900319475328460029755 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China L. Zhou 7900319475328460029756 7900319475328460029756 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China W. Wu 7900319475328460029757 7900319475328460029757 No Department of Ultrasound, Tongren Hospital of Wuhan University, Wuhan Third Hospital, Wuhan, China