MiR-107 inhibits the malignant biological behavior of esophageal squamous cell carcinoma by targeting TPM3

[摘要] Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal and aggressive tumor. Our previous study revealed that tropomyosin 3 (TPM3) is up-regulated in the late stage of ESCC and promotes epithelial-mesenchymal transition (EMT) via MMP2/MMP9. However, we have not yet explored the upstream regulator of TPM3. In this study, miR-107, a microRNA molecule, was predicted as an inhibitor targeting TPM3, and in vivo and in vitro experiments confirmed this hypothesis. Methods: Western blot and fluorescence quantitative polymerase chain reaction (qPCR) were applied to analyze the expression of miR-107 and TPM3. Flow cytometry, cell counting kit-8 (CCK8) assay, wound-healing assay, colony formation assay, transwell assay, and a BALB/c nude mouse (male, 8 weeks old, 20±2 g) model were used to detect the function of miR-107 and TPM3 in ESCC. Dual-luciferase assay was used to analyze the suppressed TPM3 expression induced by miR-107. Rescue experiments were also conducted in our research. Results: The cell and nude mouse models verified that TPM3 promotes proliferation, invasion and metastasis, and inhibits apoptosis, which is the opposite effect of miR-107 in ESCC. Meanwhile, the expression of TPM3 was up-regulated in the ESCC sample and cell lines, and miR-107 was down-regulated correspondingly. Dual-luciferase detection confirmed that miR-107 decreased the expression of TPM3 by targeting the 3’-untranslated region (3’-UTR) at the end of the TPM3 transcript. Further experiments verified that TPM3 could rescue the tumor suppression effect derived from miR-107. Conclusions: MiR-107 negatively regulates TPM3 expression and plays a tumor suppression role in ESCC.

[学科分类] 肿瘤学

[关键词] Esophageal squamous cell carcinoma (ESCC);miR-107;tropomyosin 3 (TPM3);proliferation;apoptosis