Abstract
Cutaneous squamous cell carcinoma (CSCC) is a malignant proliferation of cutaneous epithelium that has been observed to have an alarming rise in incidence. Numerous studies have demonstrated microRNAs (miRNAs or miRs) as important biomarkers in the diagnosis, prognosis, and treatment of CSCC. This study aims to investigate the effects of miR-203 on the behaviors of CSCC cells and possible mechanisms associated with protein regulator of cytokinesis-1 (PRC1) and Wnt/β-catenin signaling pathway. PRC1 was suggested as a target of miR-203 in squamous cell carcinoma cell line 1 (SCL-1) cells by dual-luciferase reporter gene assay. Based on the immunohistochemical staining and qRT-PCR, PRC1 was abundantly expressed while miR-203 was poorly expressed in CSCC tissues. miR-203 mimic or inhibitor was transfected into SCL-1 cells to upregulate or downregulate its expression. Upregulation of miR-203 downregulated PRC1 expression to block the Wnt/β-catenin signaling pathway. By conducting 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), scratch test, and Transwell and flow cytometric analyses, miR-203 was witnessed to restrain SCL-1 cell proliferation, migration, and invasion while accelerating their apoptosis. The rescue experiments addressed that inhibition of the Wnt/β-catenin signaling pathway conferred the anti-tumor effect of miR-203. These results establish a tumor-suppressive role for miR-203 in CSCC cell line SCL-1. Hence, miR-203 has promising potential as a therapeutic target for CSCC.
Highlights
Cutaneous squamous cell carcinoma (CSCC) is a malignancy of the skin characterized by the aberrant proliferation of keratinocytes.[1]
A previous study found that the abnormal expression of Protein regulator of cytokinesis-1 (PRC1) may predict recurrence of male prostate cancer, which can be used as a marker of prognosis for this malignancy.[19]
The relationship between expression of PRC1 gene and the prognosis of CSCC was retrieved from the The Cancer Genome Atlas (TCGA) database, the results of which found that the expression of PRC1 was related to the prognosis of CSCC patients (p < 0.05; Figure 1B)
Summary
Cutaneous squamous cell carcinoma (CSCC) is a malignancy of the skin characterized by the aberrant proliferation of keratinocytes.[1]. Protein regulator of cytokinesis-1 (PRC1), known as ASE1, is identified to be a mitotic spindle associated cyclin dependent kinases (CDKs) substrate that is involved in cytokinesis.[11] PRC1 contributes to tumorigenesis in lung adenocarcinoma via the activation of the Wnt/b-catenin signaling pathway.[12] The Wnt/b-catenin signaling pathway is one of the typical pathways involved in cell signal transduction, in which the phosphorylation of b-catenin is important for the signaling transduction, influencing tumorigenesis, cell multiplication, and differentiation.[13] Abnormal upregulation of b-catenin has been detected in CSCC samples.[14] The activation of the Wnt/ b-catenin signaling pathway plays a significant role in proliferation, metastasis, and apoptosis of oral squamous cell carcinoma (OSCC) cells, both in vitro and in vivo.[15] the activation of the Wnt/b-catenin signaling pathway has been reported to induce carcinogenesis and the progression of esophageal squamous cell carcinoma.[16] The present study was conducted to examine the potential role of miR-203 in the growth, migration, invasion, and apoptosis of CSCC cells, and whether miR-203 could interact with PRC1 gene and the Wnt/b-catenin signaling pathway
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