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Int J Biol Sci 2022; 18(5):1878-1895. doi:10.7150/ijbs.69934 This issue Cite

Research Paper

Radiosensitizer EXO-miR-197-3p Inhibits Nasopharyngeal Carcinoma Progression and Radioresistance by Regulating the AKT/mTOR Axis and HSPA5-mediated Autophagy

Jiahui Jiang¹, Qiao Tang², Jiaoe Gong³, WeiHong Jiang¹, Yiting Chen^1,6, Qi Zhou¹, Alaa Aldeen¹, Shuanglian Wang¹, Chengmin Li^1,4, Wuwu Lv^1,5, Tao Du¹, Xingwei Wang¹, Xueying Long⁷, Xueping Feng^1✉

1. 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.
2. 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.
3. Hunan Children's Hospital, Changsha, Hunan Province 410008, China.
4. Department of Pathology and Institute of Medical Sciences, National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.
5. Department of Oncology, The Fourth Affiliated Hospital, Zhejiang University, Yiwu, Zhejiang Province 322000, China.
6. Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha 410013, China
7. Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, China.

✉ Corresponding author: Dr Xueping Feng, 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 410008, China. Tel/Fax: +86 0731 84327069. E-mail address: Xuepfengedu.cn; fxp1029com; 522367630com. More

Abstract

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 in vitro could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression in vivo 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 in vitro, and tumor growth and radioresistance of NPC cells in vivo. 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.

Keywords: Nasopharyngeal carcinoma, Exosomes, MicroRNA, HSPA5, Radioresistant cells

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