Silencing circPVT1 enhances radiosensitivity in non-small cell lung cancer by sponging microRNA-1208

Article type: Research Article

Authors: Huang, Meifang^{a; 1} | Li, Tianqian^{a; 1} | Wang, Qing^a | Li, Chongxin^a | Zhou, Huahua^a | Deng, Shengyi^a | Lv, Zengbo^a | He, Yongmei^a | Hou, Bo^{b; *} | Zhu, Guangying^{c; d; e; *}

Affiliations: [a] Department of Oncology, The First People’s Hospital of Qujing/The Qujing Affiliated Hospital of Kunming Medical University, Qujing, Yunnan, China | [b] Department of Thoracic Surgery, The First People’s Hospital of Qujing/The Qujing Affiliated Hospital of Kunming Medical University, Qujing, Yunnan, China | [c] Department of Radiation Oncology, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China | [d] Institute of Respiratory Medicine, Chinese Academy of Medicine Sciences, Beijing, China | [e] National Center for Respiratory Disease, Beijing, China

Correspondence: [*] Corresponding authors: Bo Hou, Department of Thoracic Surgery, The First People’s Hospital of Qujing/The Qujing Affiliated Hospital of Kunming Medical University, No.1 Yuanlin Road, Qilin District, Qujing 655000, Yunnan, China. E-mail: [email protected]. Guangying Zhu, Department of Radiation Oncology, Center of Respiratory Medicine, China-Japan Friendship Hospital; Institute of Respiratory Medicine, Chinese Academy of Medicine Sciences; National Center for Respiratory Disease, No.2 Yinghuadong Street, Chaoyang, Beijing 100029, China. E-mail: [email protected].

Note: [1] Meifang Huang and Tianqian Li are co-first authors.

Abstract: BACKGROUND: Radiotherapy is one of main useful therapies in non-small cell lung cancer (NSCLC). Nevertheless, the underlying mechanism between NSCLC cell radiosensitivity and effective treatment remains unclear. OBJECTIVE: The aim is to explore the relationship between circular (circ) RNA and NSCLC cell radiosensitivity. METHODS: CircRNA plasmacytoma variant translocation 1 (PVT1) and microRNA (miR)-1208 expression in NSCLC cells were assessed using quantitative reverse transcriptase PCR (qRT-PCR). NSCLC cells were transfected with si-PVT1 or miR-1208 inhibitor and then exposed to irradiation. Cellular biology behaviors were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), colony formation, invasion and western blot. Additionally, binding between circPVT1 and miR-1208 was testified by dual-luciferase reporter and RIP assay. RESULTS: CircPVT1 was upregulated in NSCLC cells after irradiation treatment. Silencing circPVT1 induced inhibition of NSCLC cell growth and invasion, accompanied by cell apoptosis and γ-H2AX expression. Moreover, NSCLC cell proliferation and invasion was further inhibited by irradiation treatment in circPVT1-silenced cells, indicating a strong radiosensitivity of NSCLC cells. CircPVT1 functions as a competing endogenous RNA of miR-1208. Silencing miR-1208 reversed NSCLC cell sensitivity response to irradiation and activated PI3K/AKT/mTOR pathway in circPVT1-silenced cells. CONCLUSIONS: Silencing circPVT1 enhanced radiosensitivity of NSCLC cells by sponging miR-1208.

Keywords: NSCLC, circPVT1, miR-1208, radiosensitivity, PI3K/AKT/mTOR signaling

DOI: 10.3233/CBM-203252

Journal: Cancer Biomarkers, vol. 31, no. 3, pp. 263-279, 2021