Department of Otolaryngology-head and Neck Surgery, Department of Oncology and Institute of Medical Sciences, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Department of Urology and Institute of Medical Sciences, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
Int J Biol Sci. 2022 Feb 21;18(5):1878-1895. doi: 10.7150/ijbs.69934. eCollection 2022.
The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression could significantly inhibit the growth and enhance the radiosensitivity of NPC cells. From the perspective of mechanism, miR-197-3p could inhibit AKT/mTOR phosphorylation activation, inhibit an activated pathway of AKT/mTOR, target Heat Shock 70-kDa Protein 5(HSPA5) related to endoplasmic reticulum homeostasis, inhibit HSPA5-mediated autophagy, and reverse the radioresistance of NPC. Interestingly, exosomal miR-197-3p (EXO-miR-197-3p) reduced the proliferation and migration potential of NPC cells , and tumor growth and radioresistance of NPC cells . EXO-miR-197-3p inhibited NPC progression and radioresistance by regulating AKT/mTOR phosphorylation activation and HSPA5-mediated autophagy. In conclusion, our results highlight the potential of EXO-miR-197-3p as an effective radiosensitizer and therapeutic agent for refractory NPC.
外泌体和 microRNAs（miRs）在鼻咽癌（NPC）中的生物学功能在很大程度上仍未得到探索。在这里，筛选并鉴定了 miR-197-3p，其在 NPC 患者的血清和外泌体中的水平降低。miR-197-3p 可能是一种良好的诊断和预后指标。我们的数据表明，miR-197-3p 的表达与 NPC 的放射抵抗性、细胞凋亡、增殖、迁移和存活密切相关。抑制 miR-197-3p 的表达可以促进 NPC 细胞的增殖和迁移，而促进 miR-197-3p 的表达则可以显著抑制 NPC 细胞的生长并增强其放射敏感性。从机制的角度来看，miR-197-3p 可以抑制 AKT/mTOR 磷酸化激活，抑制 AKT/mTOR 的激活途径，靶向与内质网稳态相关的 Heat Shock 70-kDa Protein 5（HSPA5），抑制 HSPA5 介导的自噬，并逆转 NPC 的放射抵抗性。有趣的是，外泌体 miR-197-3p（EXO-miR-197-3p）降低了 NPC 细胞的增殖和迁移潜能，以及 NPC 细胞的肿瘤生长和放射抵抗性。EXO-miR-197-3p 通过调节 AKT/mTOR 磷酸化激活和 HSPA5 介导的自噬来抑制 NPC 的进展和放射抵抗性。总之，我们的研究结果强调了 EXO-miR-197-3p 作为治疗难治性 NPC 的有效放射增敏剂和治疗剂的潜力。
