Dataset Information

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM.

ABSTRACT: Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be up-regulated in tumorigenesis. However, comprehensive studies of KPNA2 functions in renal cell carcinoma (RCC) are still lacking. In this study, we aim to investigate the roles of KPNA2 in kidney tumour development. Our results showed that down-regulation of KPNA2 inhibited the proliferation and invasion of kidney tumour cell cells in vitro, while the cell cycle arrest and cellular apoptosis were induced once KPNA2 was silenced. Repression of KPNA2 was proved to be efficient to repress tumorigenesis and development of kidney tumour in in nude mice. Furthermore, one related participator, NPM, was identified based on Co-IP/MS and bioinformatics analyses. The up-regulation of NPM attenuates the efficiency of knockdown KPNA2. These results indicated that KPNA2 may regulate NPM to play a crucial role for kidney tumour development.

SUBMITTER: Zheng S

PROVIDER: S-EPMC8500977 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM.

Zheng Song S Li Xiaofan X Deng Ting T Liu Rong R Bai Junjie J Zuo Teng T Guo Yinan Y Chen Jianhui J

Journal of cellular and molecular medicine 20210901 19

Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be up-regulated in tumorigenesis. However, comprehensive studies of KPNA2 functions in renal cell carcinoma (RCC) are still lacking. In this study, we aim to investigate the roles of KPNA2 in kidney tumour development. Our results showed that down-regulation of KPNA2 inhibited the proliferation and invasion of kidney tumour cell cells in vitro, while the cell cycle arrest and cellular apoptosis were induced onc ...[more]

PMID: 34469024

Similar Datasets

Project description:IntroductionAccumulating evidence has demonstrated that circular RNAs (circRNAs) play a key role in the tumorigenesis of various types of cancers, including clear cell renal cell carcinoma (ccRCC).Materials and methodsReverse transcription-quantitative polymerase chain reaction was used to detect the expression of circRNA homeodomain interacting protein kinase 3 (circHIPK3) and microRNAs (miRNAs), including miR-508-3p. The clinical measurement of circHIPK3 was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic analysis. Cell Counting Kit-8 and Transwell chamber assays were performed to determine the changes in the proliferative and metastatic ability of A498 and 786-O cells. C-X-C motif chemokine ligand 13 (CXCL13) protein expression was detected by Western blot analysis. The targeted binding effect between miR-508-3p and circHIPK3 or CXCL13 was confirmed by constructed luciferase and RNA immunoprecipitation (RIP) assays, respectively. Fluorescence in situ hybridization (FISH) assay was used to measure the subcellular localization of circHIPK3 and miR-508-3p.ResultsIt was found that circHIPK3 was markedly upregulated in ccRCC tissue and cell lines, and circHIPK3-upregulation was closely correlated with poor clinicopathological features in patients with ccRCC. It was found that both miR-508-3p and circHIPK3 were localized in the cytoplasm of ccRCC cells. The up- and downregulation of circHIPK3 positively regulated ccRCC cell proliferation and metastasis, and this regulatory effect was reversed by miR-508-3p. Through luciferase and RIP assays, it was confirmed that circHIPK3 could interacted with miR-508-3p. Furthermore, it was revealed that CXCL13, which was negatively correlated with miR-508-3p, was upregulated in ccRCC. It was also shown that CXCL13 was a downstream target of miR-508-3p. miR-508-3p suppressed ccRCC cell proliferation and metastasis by targeting CXCL13. Lastly, it was demonstrated that circHIPK3 promoted CXCL13 to facilitate ccRCC cell proliferation and metastasis by decoying miR-508-3p.ConclusionIn brief, the results of the present study showed that circHIPK3 promoted ccRCC cell proliferation and metastasis by altering miR-5083p/CXCL13 signaling. The present findings might provide a novel target for the molecular treatment of ccRCC.

Project description:BackgroundAGBL2's role in tumorigenesis and cancer progression has been reported in several cancer studies, and it is closely associated with α-tubulin detyrosination. The roles of AGBL2 and α-tubulin detyrosination in renal cell carcinoma (RCC) pathogenesis remain unclear and require further investigation.MethodsIn this study, we conducted an analysis of AGBL2 expression differences between renal clear cell carcinoma tissues and normal tissues using data from The Cancer Genome Atlas (TCGA). We performed a comprehensive prognostic analysis of AGBL2 in Kidney Renal Clear Cell Carcinoma (KIRC) using univariate and multivariate Cox regression. Based on the results of the Cox analysis, we constructed a prognostic model to assess its predictive capabilities. Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of AGBL2 in renal cancer. We conducted further validation by analyzing cancer tissue samples and renal cancer cell lines, which confirmed the role of AGBL2 in promoting RCC cell proliferation and migration through in vitro experiments. Additionally, we verified the impact of AGBL2's detyrosination on α-tubulin using the tubulin carboxypeptidase (TCP) inhibitor parthenolide. Finally, we performed sequencing analysis on AGBL2 knockdown 786-O cells to investigate the correlation between AGBL2, immune infiltration, and AKT phosphorylation. Moreover, we experimentally demonstrated the enhancing effect of AGBL2 on AKT phosphorylation.ResultsTCGA analysis revealed a significant increase in AGBL2 expression in RCC patients, which was correlated with poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). According to the analysis results, we constructed column-line plots to predict the 1-, 3-, and 5-year survival outcomes in RCC patients. Additionally, the calibration plots assessing the model's performance exhibited favorable agreement with the predicted outcomes. And the ROC curves showed that AGBL2 showed good diagnostic performance in KIRC (AUC = 0.836)). Cell phenotyping assays revealed that AGBL2 knockdown in RCC cells significantly inhibited cell proliferation and migration. Conversely, overexpression of AGBL2 resulted in increased cell proliferation and migration in RCC cells. We observed that AGBL2 is predominantly located in the nucleus and can elevate the detyrosination level of α-tubulin in RCC cells. Moreover, the enhancement of RCC cell proliferation and migration by AGBL2 was partially inhibited after treatment with the TCP inhibitor parthenolide. Analysis of the sequencing data revealed that AGBL2 is associated with a diverse array of biological processes, encompassing signal transduction and immune infiltration. Interestingly, AGBL2 expression exhibited a negative correlation with the majority of immune cell infiltrations. Additionally, AGBL2 was found to enhance the phosphorylation of AKT in RCC cells.ConclusionOur study suggests that AGBL2 fosters RCC cell proliferation and migration by enhancing α-tubulin detyrosination. Moreover, elevated AGBL2 expression increases phosphorylation of AKT in RCC cells.

Dataset Information

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM.

Publications

KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets