Lung squamous cell carcinoma (LUSC) is one of the major subtypes of lung cancer. Non-SMC condensin I complex subunit H (NCAPH) is highly regarded as a valuable biomarker in certain malignant tumors. However, the specific roles of NCAPH in LUSC are not well understood. The objective of this work was to determine the effect of NCAPH on the progression of LUSC and to identify the microRNAs (miRNAs) located upstream of NCAPH that regulate its function. MicroRNA and mRNA expression profiles, as well as clinical data of LUSC (Normal: 49, LUSC: 502), were obtained from the TCGA database for the purpose of differential analysis and survival analysis. The expression of NCAPH and miR-1976 in LUSC cell lines was detected using Quantitative reverse transcription PCR (qRT-PCR) and western blot techniques. In this study, the impact of NCAPH on the proliferation of LUSC cells was assessed using CCK-8 and colony formation assay. Additionally, the effects of NCAPH on the migration and invasion of LUSC cells were evaluated using the Transwell assay. Furthermore, the effects of NCAPH on the apoptosis of LUSC cells were evaluated using flow cytometry. The target miRNAs of NCAPH were predicted using bioinformatics, and the targeting link between miR-1976 and NCAPH was confirmed using a dual-luciferase reporter gene experiment. The findings indicated that the expression of NCAPH was notably elevated in LUSC tissues ( P < 0.05), while the expression of its upstream miRNA (miR-1976) was notably reduced ( P < 0.05). The dual-luciferase test results indicated that miR-1976 functions as an upstream target miRNA of NCAPH. Low expression of NCAPH may inhibit the proliferation ( P < 0.05), migration ( P < 0.05), invasion ( P < 0.05), and promote apoptosis ( P < 0.05) in LUSC cells. However, the suppression of miR-1976 may reverse this inhibitory effect by specifically targeting NCAPH. This study showed that NCAPH can serves as a novel potential oncogenic biomarker for LUSC and its regulation is controlled by upstream miR-1976. miR-1976 can directly targets NCAPH to affect the proliferation, migration, invasion, and apoptosis of LUSC cell.
Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is associated with the progression of several human malignancies. However, its role in lung squamous cell carcinoma (LUSC) remains unclear. We measured STEAP3 expression in LUSC cell lines and tissues. LUSC cells with stable STEAP3 overexpression and knockdown were obtained through G418 selection. Multiple assays were used to evaluate the malignant phenotypes of LUSC cells and the activation of the β-catenin signaling. The potential transcriptional regulatory factors of STEAP3 were predicted using the JASPAR database, and the correlation between transcription factor AP-2 gamma (TFAP2C) and STEAP3 was analyzed through the GEPIA database. The study evaluated the regulatory relationship between a potential transcription factor and STEAP3 through ChIP and luciferase reporter assays. Additionally, rescue assays were utilized to ascertain whether TFAP2C serves as the upstream regulatory factor of STEAP3, contributing to LUSC progression. Finally, tumor growth and metastasis were evaluated in vivo. STEAP3 expression was notably higher in LUSC, and its overexpression was linked to a poor prognosis. Moreover, STEAP3 overexpression activated the β-catenin pathway, thereby accelerating cell proliferation and metastasis. Conversely, STEAP3 knockdown had an anti-tumor effect in LUSC. Additionally, TFAP2C bound directly to the STEAP3 promoter and positively regulate its expression in LUSC. The anti-tumor effects of TFAP2C knockdown were partially reversed by STEAP3 overexpression. The study indicates that the TFAP2C/STEAP3 axis may be a therapeutic target for LUSC treatment. This enhances our understanding of lung carcinogenesis.
危险品化学品经营许可证（带存储）