Zhu Xiaofeng, Xie Minghua, Cui Yayun
Department of Gastroenterology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, 230031, Anhui, China.
Department of Thoracic Surgery, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei, 230031, Anhui, China.
J Cardiothorac Surg. 2025 Jul 14;20(1):298. doi: 10.1186/s13019-025-03528-1.
Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal malignancy characterized by a high incidence and mortality rate. ESCC frequently develops drug resistance during chemotherapy, resulting in diminished clinical efficacy. Previous studies have identified SNHG16, a long non-coding RNA, as a crucial oncogene, but its underlying mechanisms in the biological functions and chemoresistance regulation in ESCC remain unclear.
RT-qPCR and western blotting were utilized to detect SNHG16, miR-497-5p, and HK2 expression in DDP-resistant/sensitive ESCC tissues and cells. In vitro functional experiments were performed by transfecting DDP-resistant ESCC cells lines with sh-SNHG16, including CCK8, flow cytometry, EdU assay, and transwell assay. Mechanistically, the mechanistic aspects and target binding relationship were established through the luciferase reporter assay. In vivo xenograft model was established to examine the impact of SNHG16.
SNHG16 was significantly overexpressed in both DDP-resistant ESCC tissues and cells. Functional in vitro studies demonstrated that silencing SNHG16 significantly inhibited the proliferation, migration and invasion of ESCC cells, induced cell apoptosis, and sensitized DDP-resistant cells to DDP. Moreover, SNHG16 exerted malignant biological behavior in ESCC cells and conferred cisplatin resistance by acting as a sponge for miR-497-5p and regulating HK2.
Our findings uncovered that SNHG16 promoted ESCC malignant progression and DDP resistance through the miR-497-5p/HK2 axis, laying the groundwork for deciphering the molecular mechanisms underlying chemotherapy resistance in ESCC and developing new treatment strategies.
食管鳞状细胞癌（ESCC）是一种常见的胃肠道恶性肿瘤，具有高发病率和死亡率的特点。ESCC在化疗过程中经常产生耐药性，导致临床疗效降低。先前的研究已确定长链非编码RNA SNHG16是一种关键的癌基因，但其在ESCC生物学功能和化疗耐药性调控中的潜在机制仍不清楚。
采用RT-qPCR和蛋白质免疫印迹法检测顺铂耐药/敏感的ESCC组织和细胞中SNHG16、miR-497-5p和HK2的表达。通过用sh-SNHG16转染顺铂耐药的ESCC细胞系进行体外功能实验，包括CCK8、流式细胞术、EdU检测和Transwell检测。从机制上，通过荧光素酶报告基因检测确定其机制及靶标结合关系。建立体内异种移植模型以检测SNHG16的影响。
SNHG16在顺铂耐药的ESCC组织和细胞中均显著过表达。体外功能研究表明，沉默SNHG16可显著抑制ESCC细胞的增殖、迁移和侵袭，诱导细胞凋亡，并使顺铂耐药细胞对顺铂敏感。此外，SNHG16通过充当miR-497-5p的海绵并调节HK2，在ESCC细胞中发挥恶性生物学行为并赋予顺铂耐药性。
我们的研究结果揭示了SNHG16通过miR-497-5p/HK2轴促进ESCC的恶性进展和顺铂耐药性，为阐明ESCC化疗耐药的分子机制和开发新的治疗策略奠定了基础。
