Transcription factor HOXC13 promotes malignant biological behaviors of laryngeal squamous cell carcinoma by upregulating PCNA expression
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Abstract:
Objective: To investigate the expression, function and possible regulatory mechanisms of transcription factor HOXC13 in laryngeal squamous cell carcinoma (LSCC). Methods: LSCC cells were routinely cultured and divided into sh-NC group, sh-HOXC13 group, pcDNA3.1-NC group, pcDNA3.1-HOXC13 group, pcDNA3.1-PCNA group, and sh-HOXC13+pcDNA3.1-PCNA group, and the corresponding nucleic acids and plasmids were transfected into each group of cells with transfection reagents. GEO Database data were used to analyze the expression of HOXC13 mRNA in LSCC tissues. Sixty-two pairs of LSCC tissues and paired adjacent tissues that were surgically removed in the 980th Hospital of the Joint Logistics Support Force between January 2019 and December 2022 were collected. The expression of HOXC13 protein in Chinese LSCC tissues were detected by immunohistochemistry. The expressions of HOXC13 and PCNA mRNA in Chinese LSCC tissues, adjacent non-cancerous tissues, and various cell lines were detected by qPCR. The proliferation ability of AMC-HN-8 cells in different groups was detected by the MTS method. Plate cloning assay was used to detect the clone formation ability of transfected AMC-HN-8 cells in each group. The migration and invasion abilities of AMC-HN-8 cells in each group were determined by transwell chamber experiments. The binding relationship between HOXC13 and PCNA was verified by dual luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) techniques. Results: HOXC13 and PCNA were highly expressed in LSCC tissues and cells (P<0.05 or P<0.01). Their expression levels were positively correlated (P<0.01), and the expression level of HOXC13 was significantly correlated with TNM stage (P<0.01). Knockdown of HOXC13 significantly inhibited the proliferation, migration and invasion abilities of AMC-HN-8 cells (all P<0.01), and overexpression of HOXC13 promoted the proliferation, migration and invasion abilities of TU686 cancer cells (all P<0.01). HOXC13 could bind to the promoter region of PCNA and regulate its transcription. Knockdown of PCNA partially reversed the promotion of HOXC13 on the malignant biological behaviors of AMC-HN-8 cells (all P<0.01). Conclusion: HOXC13 promotes the malignant biological behaviors of LSCC cells by upregulating PCNA. HOXC13 is a potential target for clinical diagnosis and treatment of LSSC.