MicroRNA-141-3p inhibits the progression of oral squamous cell carcinoma via targeting PBX1 through the JAK2/STAT3 pathway

MicroRNA-141-3p 通过 JAK2/STAT3 通路靶向 PBX1 抑制口腔鳞状细胞癌进展

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作者:Mingguo Cao, Kebin Tian, Weifeng Sun, Jun Xu, Yu Tang, Shilian Wu

Abstract

Oral squamous cell carcinoma (OSCC), which is the most common epithelial malignant neoplasm in the head and neck, is characterized by local infiltration and metastasis of lymph nodes. The five-year survival rate of OSCC remains low despite the advances in clinical methods. miR-141-3p has been shown to activate or inhibit tumorigenesis. However, the effects of miR-141-3p on invasion and migration of OSCC remain unclear. The present study aimed to evaluate the effects of miR-141-3p on invasion, proliferation, and migration in oral squamous cell carcinoma (OSCC). Reverse transcription quantitative PCR, western blotting and immunohistochemistry were used to detect microRNA(miR)-141-3p and pre-B-cell leukaemia homeobox-1 (PBX1) expression in OSCC tissues and cell lines. The luciferase reporter assay was used to detect targets of miR-141-3p in OSCC. MTT, Transwell and wound healing assays were used to determine the cell proliferation and invasive and migratory abilities, respectively. Expression of constitutive phosphorylated (p)-Janus kinase 2 (JAK2) and p-signal transducer and activator of transcription 3 (STAT3) was detected using western blotting in tissues and cells. miR-141-3p expression was decreased in OSCC tissues and cells, while PBX1 protein expression was increased compared with non-cancerous controls. The result from the dual-luciferase reporter assay revealed that PBX1 was the direct target of miR-141-3p in OSCC tissues. Furthermore, miR-141-3p overexpression and PBX1 knockdown could reduce cell invasion, proliferation and migration, and inhibit the JAK2/STAT3 pathway; however, miR-141-3p downregulation had the opposite effects. In addition, silencing of PBX1 using small interfering RNA could weaken the effects of miR-141-3p inhibitor on JAK2/STAT3 pathway and cell progression in CAL27 cells. In summary, the findings from this study indicated that miR-141-3p upregulation could inhibit OSCC cell invasion, proliferation and migration, by targeting PBX1 via the JAK2/STAT3 pathway.

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