ABSTRACT
Dysregulated expression of ubiquitin-specific protease 43 (USP43) has been recently discovered in malignancies. This study aimed to investigate the expression pattern of USP43 protein in lung squamous cell carcinoma (LUSC) and to explore its correlation with patients' clinicopathological characteristics as well as clinical outcomes. Expression of USP43 protein was determined by immunohistochemistry staining in a retrospective cohort containing 157 LUSC cases who underwent curative surgery in our hospital. Accordingly, USP43 protein was positively correlated with tumor size, depth of invasion, and lymph node metastasis. Patients with increased USP43 expression or positive lymph nodes exhibited a poorer overall survival. In addition, cellular assays elucidated that USP43 can promote LUSC growth and invasion. Taken together, our study demonstrated that USP43 may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the survival prediction and treatment of LUSC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Ubiquitin Thiolesterase , Carcinogenesis , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Prognosis , Retrospective Studies , Ubiquitin Thiolesterase/genetics , Ubiquitin Thiolesterase/metabolismABSTRACT
OBJECTIVE: Exosomes can convey particular microRNAs (miRNAs) to affect biological functions of cancer cells. Nevertheless, the impact of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-exos) transmitting miR-19b-3p on esophageal cancer (EC) progression remains scarcely studied. We aimed to explore the role of BMSC-exos mediating miR-19b-3p in EC cell growth. METHODS: Eighty-three cases of EC patients were included in this study and the expression of miR-19b-3p and suppressor of cytokine signaling 1 (SOCS1) in cancer and adjacent normal tissues from the patients were assessed. BMSCs were cultured and BMSC-exos were extracted, which were then transfected with altered miR-19b-3p and SOCS1 to assess their roles in proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and apoptosis of EC cells. Targeting relationship between miR-19b-3p and SOCS1 was verified by Targetscan and dual luciferase reporter gene assay. MiR-19b-3p and SOCS1 expression was assessed in TE-2 cells. RESULTS: MiR-19b-3p was upregulated and SOCS1 was downregulated in EC tissues. BMSC-exos or exosomal miR-19b-3p promoted malignant behaviors of EC cells. MiR-19b-3p was upregulated and targeted SOCS1 in EC cells. MiR-19b-3p inhibition or SOCS1 overexpression suppressed proliferation, migration, invasion and EMT, and induced apoptosis of EC cells. SOCS1 silencing abrogated these effect of miR-19b-3p inhibition on EC cells. CONCLUSION: BMSC-derived exosomal miR-19b-3p promotes progression of EC through targeting SOCS1. This study provides a novel understanding on molecular mechanisms of EC.
