Zeng Can, Duan Shuangni, Zhao Lin, Jiang Jing
School of Public Health, Xiangnan University, Chenzhou, China.
Yuelu District Center for Disease Control and Prevention, Changsha, China.
Biochem Genet. 2025 Feb;63(1):713-729. doi: 10.1007/s10528-024-10741-5. Epub 2024 Mar 21.
Radiotherapy resistance is a major cause of treatment failure and leads to poor prognosis in nasopharyngeal carcinoma (NPC). Evidences indicate that microRNA (miRNAs) are closely associated with radiotherapy for NPC. In this study, we found that the expression level of miR-92b-3p was significantly higher in radiotherapy-sensitive NPC patients than in radiotherapy-resistant patients. High expression of miR-92b-3p was associated with good prognosis in patients with NPC, and high expression of FHL2 was associated with poor prognosis in patients with NPC. It was predicted that miR-92b-3p could directly target and bind FHL2. Overexpression of miR-92b-3p significantly inhibited FHL2 expression at the mRNA as well as protein levels, while inhibition of miR-92b-3p expression significantly upregulated FHL2 expression. Overexpression of miR-92b-3p significantly reduced proliferation and colony formation in NPC cells. Inhibition of miR-92b-3p attenuated the sensitivity of nasopharyngeal carcinoma to radiotherapy, while simultaneous inhibition of miR-92b-3p and FHL2 increased the sensitivity of NPC to radiotherapy. Our findings highlighted that miR-92b-3p is closely associated with radiotherapy sensitivity and prognosis in NPC patients and may improve the sensitivity of NPC to radiotherapy by targeting FHL2.
放射治疗抵抗是鼻咽癌（NPC）治疗失败的主要原因，并导致预后不良。有证据表明，微小RNA（miRNA）与鼻咽癌的放射治疗密切相关。在本研究中，我们发现miR-92b-3p在放射治疗敏感的鼻咽癌患者中的表达水平显著高于放射治疗抵抗的患者。miR-92b-3p的高表达与鼻咽癌患者的良好预后相关，而FHL2的高表达与鼻咽癌患者的不良预后相关。据预测，miR-92b-3p可直接靶向并结合FHL2。miR-92b-3p的过表达在mRNA和蛋白质水平上均显著抑制FHL2的表达，而抑制miR-92b-3p的表达则显著上调FHL2的表达。miR-92b-3p的过表达显著降低了鼻咽癌细胞的增殖和集落形成。抑制miR-92b-3p减弱了鼻咽癌对放射治疗的敏感性，但同时抑制miR-92b-3p和FHL2则增加了鼻咽癌对放射治疗的敏感性。我们的研究结果突出表明，miR-92b-3p与鼻咽癌患者的放射治疗敏感性和预后密切相关，并且可能通过靶向FHL2提高鼻咽癌对放射治疗的敏感性。
