Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China; Department of Pathology, Henan Provincial People's Hospital, Zhengzhou 450001, China.
Department of Pathophysiology, College of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Cell Signal. 2023 Dec;112:110906. doi: 10.1016/j.cellsig.2023.110906. Epub 2023 Sep 23.
Esophageal cancer is one of the most malignant gastrointestinal malignancies. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China. In recent years, with developments in basic medicine, it has been demonstrated that the abnormal expression of circular RNA (circRNA) plays an important role in the progression and prognosis of ESCC. This study explored the role and downstream molecular mechanisms of circ_0046534 in ESCC. We identified circ_0046534, which was found to be highly expressed in ESCC tissues and cells. Moreover, the downregulation of circ_0046534 inhibited the proliferation, migration and invasion of ESCC cells and the growth and metastasis of ESCC tumours in vivo. Dual-luciferase reporter assays showed that circ_0046534 sponged miR-339-5p and inhibited the expression of miR-339-5p. Furthermore, MMP2 was identified to be a direct target of miR-339-5p through bioinformatics analysis. In addition, the knockdown of circ_0046534 inhibited the expression of the downstream target gene matrix metalloproteinase 2 (MMP2) by releasing the adsorption of miR-339-5p. Taken together, this study demonstrated that silencing circ_0046534 inhibited the growth and metastasis of ESCC through the miR-339-5p/MMP2 pathway. Circ_0046534 is expected to serve as a new biomarker and target for ESCC and provide a new direction for its diagnosis and treatment.
食管癌是最恶性的胃肠道恶性肿瘤之一。食管鳞状细胞癌（ESCC）是中国最常见的食管癌类型。近年来，随着基础医学的发展，已经证明环状 RNA（circRNA）的异常表达在 ESCC 的进展和预后中起着重要作用。本研究探讨了 circ_0046534 在 ESCC 中的作用及其下游分子机制。我们鉴定了 circ_0046534，发现其在 ESCC 组织和细胞中高表达。此外，circ_0046534 的下调抑制了 ESCC 细胞的增殖、迁移和侵袭以及 ESCC 肿瘤在体内的生长和转移。双荧光素酶报告基因实验表明，circ_0046534 海绵吸附 miR-339-5p 并抑制 miR-339-5p 的表达。此外，通过生物信息学分析鉴定出 MMP2 是 miR-339-5p 的直接靶基因。此外，circ_0046534 的敲低通过释放 miR-339-5p 的吸附抑制下游靶基因基质金属蛋白酶 2（MMP2）的表达。总之，本研究表明沉默 circ_0046534 通过 miR-339-5p/MMP2 通路抑制 ESCC 的生长和转移。Circ_0046534 有望成为 ESCC 的新生物标志物和治疗靶点，为其诊断和治疗提供新方向。
