Dataset Information

KMT2A regulates cervical cancer cell growth through targeting VDAC1.

ABSTRACT: Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7288919 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundEmerging evidence has identified miR-138 as a tumor suppressor that can suppress the proliferation of various cancers. Meanwhile, the cause of abnormal miR-138 expression in cervical cancer remains uncertain. This study clarified the mechanism by which miR-138 regulates proliferation, invasion, metastasis, and EMT in cervical cancer cells.ResultsmiR-138 expression in human cervical cancer and adjacent normal tissue was measured using qPCR. SiHa and C33A cells were used to determine the function of miR-138 via miR-138 mimic or inhibitor transfection, followed by wound healing, Cell Counting Kit-8, flow cytometry, and Transwell assays. Epithelial and mesenchymal marker expression was analyzed using Western blotting. DNA methylation in the miR-138 promoter was examined using bisulfite sequencing PCR. The downstream target genes of miR-138 were identified via bioinformatics analysis and luciferase reporter assays. A tumor xenograft model was employed to validate DNA methylation-induced miR-138 downregulation and tumor growth inhibition in cervical cancer in vivo. miR-138 levels were significantly lower in cervical cancer tissues than in adjacent control tissues. Furthermore, lower miR-138 expression and higher CpG methylation in the miR-138 promoter were identified in lymph node-positive metastatic cervical cancer tumors versus that in non-metastatic tumor tissues. Upon miR-138 overexpression, cell proliferation, metastasis, invasion, and EMT were suppressed. miR-138 agomir transfection and demethylating drug treatment significantly inhibited cervical tumor growth and EMT in tumor xenograft models. DNA methylation inhibited miR-138 transcription, and enhancer of zeste homolog 2 (EZH2) downregulation mediated the tumor suppressor function of miR-138 in cervical cancer.ConclusionWe demonstrated that miR-138 suppresses tumor progression by targeting EZH2 in cervical cancer and uncovered the role of DNA methylation in the miR-138 promoter in its downregulation. These findings demonstrated the potential of miR-138 to predict disease metastasis and/or function as a therapeutic target in cervical cancer.

Dataset Information

KMT2A regulates cervical cancer cell growth through targeting VDAC1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets