miR-let-7a-5p靶向调控SNAP23影响食管鳞状细胞癌发展的研究

doi:10.3969/j.issn.1004-616x.2025.01.011

Abstract

Abstract: OBJECTIVE： To explore the effect of miR-let-7a-5p on malignant development of esophageal squamous cell carcinoma (ESCC) by targeting and regulating the synaptosomal-associated protein of 23 kDa (SNAP23). METHODS： From database of Differentially Expressed MiRNAs in human Cancers (dbDEMC)， the expression levels of miR-let-7a-5p in cancer tissues and normal tissues adjacent to tumor were analyzed. From the database of MiRNAs in human Cancers (CancerMIRNome)，Kaplan-Meier survival curve and logarithmic rank test were used to investigate the relationship between the expression level of miR-let-7a-5p and the prognosis of patients with esophagea l cancer. Quantitative real-time reverse transcription-PCR (RT-qPCR) was used to detect the expression of miR-let-7a-5p in the human immortalized esophageal epithelial cell lines，SHEE and ESCC. Lentiviral vector transfection technology was utilized to construct stably transfected cell lines overexpressing miR-let-7a-5p. Cell proliferation was detected by the EdU cell proliferation and clone formation assay. Cell migration was detected by the cell scratch assay. The transwell assay was used to detect cell invasion. The expression of miR-let-7a-5p in peripheral blood of patients with esophageal cancer was analyzed in dbDEMC and CancerMIRNome databases. The downstream target genes of miR-let-7a-5p were searched in ENCORI，Diana Tarbase and miRDB databases. Protein expression of SNAP23 was detected by protein blotting (Western blot)；dual luciferase reporter gene assay was used to analyze the targeting relationship between miR-let-7a-5p and SNAP23. RESULTS： The expression level of miR-let-7a-5p in esophageal cancer tissues was lower than that in adjacent normal tissues，and the expression level was positively correlated with the overall survival of patients (P<0.05). The expression of miR-let-7a-5p in ESCC cell line was lower than that in human immortal SHEE (P<0.01). The proliferation，clone formation，migration and invasion abilities of TE-13 were significantly inhibited by enhanced miR-let-7a-5p expression compared with control (P<0.05 or P<0.01). In peripheral blood of ESCC patients，the expression level of miR-let-7a-5p was increased compared with that of healthy controls. The secreted protein SNAP23 was predicted to be the downstream target gene of miR-let-7a-5p. The protein expression level of SNAP23 decreased after overexpression of miR-let-7a-5p (P<0.01). The results of dual luciferase reporter gene assay showed that miR-let-7a-5p could down-regulate the relative luciferase activity of wild-type SNAP23 (P<0.01). CONCLUSION： miR-let-7a-5p can inhibit the malignant biological behavior of ESCC by down-regulating the expression of SNAP23.

Key words: esophageal squamous cell carcinoma, miR-let-7a-5p, SNAP23, invasive metastasis, targeted therapy

CLC Number:

R735.1

CHEN Jiao, LIU Qing, HUANG Conggai, ZHENG Shutao, LIU Tao, LU Xiaomei. miR-let-7a-5p targeted regulation of SNAP23 and malignant progression of esophageal squamous cell carcinoma[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 63-71.

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miR-let-7a-5p targeted regulation of SNAP23 and malignant progression of esophageal squamous cell carcinoma

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