BUB1-deficiency suppresses kidney renal clear cell carcinoma progression via the PI3K/Akt pathway: A bioinformatics-oriented validating study.

IF 2.3 3区 生物学 Q3 BIOCHEMICAL RESEARCH METHODS Molecular and Cellular Probes Pub Date : 2025-03-11 DOI:10.1016/j.mcp.2025.102024
Xiaolin Zi, Jinpeng Ma, Xiaoxia Li, Honglei Wang, Yuchen Bao, Tao Deng, Xueli Yuan
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引用次数: 0

Abstract

Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), the advancement of therapeutic strategies for KIRC in clinical practices have been seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing the datasets from the online UCSC database, a novel BUB1 gene was found to be elevated in the cancerous tissues compared to their normal tissues of KIRC, and and KIRC patients with high-expressed BUB1 tended to have a worse prognosis. The subsequent experiments validated that BUB1 protein was located in both nucleus and cytoplasm of KIRC cells, and the expression levels of BUB1 gene were significantly elevated in KIRC tissues and cells, in contrast to their normal counterparts. Loss-of-function experiments verified that knockdown of BUB1 suppressed cell proliferation, mobility, epithelial-mesenchymal transition (EMT) and tumor growth, whereas induced apoptotic cell death in the KIRC cells in vitro and in vivo. In addition, bioinformatics analysis predicted that the differentially-expressed genes (DEGs) in the BUB1-deficient cohorts were enriched in the cell division-related PI3K/Akt signal pathway, and we evidenced that silencing of BUB1 was capable of inactivating the downstream PI3K/Akt signal pathway. Of note, deficiency of BUB1-induced suppressing effects on the malignant phenotypes in KIRC cells were all reversed by co-treating cells with PI3K/Akt pathway activator 740Y-P. Furthermore, it was found that the expression status of BUB1 gene were related with epigenetic modifications, immune infiltration and immunotherapy responses in KIRC. Collectively, silencing of BUB1 inhibited the progression of KIRC through inactivating the downstream PI3K/Akt signal pathway, and BUB1 gene could be potentially used as biomarkers for the diagnosis and treatment of KIRC in clinic.

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来源期刊
Molecular and Cellular Probes
Molecular and Cellular Probes 生物-生化研究方法
CiteScore
6.80
自引率
0.00%
发文量
52
审稿时长
16 days
期刊介绍: MCP - Advancing biology through–omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.
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BUB1-deficiency suppresses kidney renal clear cell carcinoma progression via the PI3K/Akt pathway: A bioinformatics-oriented validating study. Corrigendum to "Identification of circRNA-mediated competing endogenous RNA network involved in the development of cervical cancer" [Mol. Cell. Probes. 78 (2024) 101984]. Down-regulated circ_0001853 inhibits lipopolysaccharide-induced endometritis progression via sponging miR-34c-5p. Silymarin plus doxorubicin exerts the anti-hepatocellular carcinoma effects via Wnt, apoptosis, autophagy and angiogenesis pathways Clinical value of microRNA-4449 of non-small cell lung cancer patients undergoing thoracic paravertebral block thoracotomy
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