Bai Lu, Zhang Jingjing, Gao Dongqi, Liu Chengyi, Li Wenxin, Li Qingshan
Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei 067000, P.R. China.
Exp Ther Med. 2021 Jul;22(1):679. doi: 10.3892/etm.2021.10111. Epub 2021 Apr 25.
High mobility group box 1 (HMGB1) has been reported to regulate the sensitivity of several types of cancer cell to chemoradiotherapy. The present study aimed to investigate the changes in HMGB1 expression after radiotherapy, as well as its regulatory role in the radiosensitivity of non-small cell lung cancer (NSCLC) cells. The expression levels of HMGB1 in the serum of 73 patients with NSCLC were analyzed by ELISA. HMGB1 mRNA and microRNA (miR)-107 expression in NSCLC cells were assessed using reverse transcription-quantitative PCR. Receiver operating characteristic analysis was used to evaluate the diagnostic value of HMGB1. Cell counting kit-8, Transwell invasion and clonogenic assays were used to determine cellular viability, invasiveness and colony formation ability, respectively. Following radiotherapy, the levels of HMGB1 were significantly decreased in the serum of patients with NSCLC, and lower serum levels had relatively high diagnostic accuracy in radiosensitive patients. Furthermore, HMGB1-knockdown retarded cellular proliferation and invasion with or without irradiation, and enhanced NSCLC cell radiosensitivity. Furthermore, knocking down miR-107 reversed the decreases in cellular proliferation and invasiveness both with and without irradiation, and reduced the survival fractions induced by sh-HMGB1. HMGB1-knockdown leads to radiosensitivity that may result from suppression of the Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Collectively, decreased expression of HMGB1 was found to be a putative diagnostic predictor of radiosensitivity in patients with NSCLC. HMGB1-knockdown inhibited the proliferation and enhanced the radiosensitivity of NSCLC cells, which may be regulated via miR-107 by mediating the TLR4/NF-κB signaling pathway. Thus, HMGB1 may be a potential regulator of radioresistance in NSCLC, and the HMGB1/miR-107 axis may represent a promising therapeutic target.
据报道，高迁移率族蛋白B1（HMGB1）可调节多种癌细胞对放化疗的敏感性。本研究旨在探讨放疗后HMGB1表达的变化及其对非小细胞肺癌（NSCLC）细胞放射敏感性的调节作用。采用酶联免疫吸附测定（ELISA）分析73例NSCLC患者血清中HMGB1的表达水平。运用逆转录定量聚合酶链反应评估NSCLC细胞中HMGB1信使核糖核酸（mRNA）和微小核糖核酸（miR）-107的表达。采用受试者工作特征分析评估HMGB1的诊断价值。分别运用细胞计数试剂盒-8、Transwell侵袭实验和克隆形成实验测定细胞活力、侵袭能力和集落形成能力。放疗后，NSCLC患者血清中HMGB1水平显著降低，较低的血清水平对放射敏感患者具有较高的诊断准确性。此外，敲低HMGB1可抑制细胞增殖和侵袭，无论是否进行照射，均可增强NSCLC细胞的放射敏感性。此外，敲低miR-107可逆转照射和未照射情况下细胞增殖和侵袭能力的降低，并降低短发夹RNA-HMGB1（sh-HMGB1）诱导的存活分数。敲低HMGB1可导致放射敏感性增加，这可能是由于Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路受到抑制所致。总体而言，发现HMGB1表达降低可能是NSCLC患者放射敏感性的诊断预测指标。敲低HMGB1可抑制NSCLC细胞增殖并增强其放射敏感性，这可能通过miR-107介导TLR4/NF-κB信号通路进行调节。因此，HMGB1可能是NSCLC放射抗性的潜在调节因子，HMGB1/miR-107轴可能是一个有前景的治疗靶点。
