Inverse correlation of miR-27a-3p and CDH5 expression serves as a diagnostic biomarker of proliferation and metastasis of clear cell renal carcinoma

Wang, Yifang; Zhou, Xiaohui; Han, Peipei; Lu, Yunliang; Zhong, Xuemin; Yang, Yanping; Li, Danping; Liu, De-Ling; Li, Qiuyun; Pan, Nenghui; Mo, Yuchang; Luo, Wenqi; Li, Ping; Zhou, Xiaoying; Matskova, Liudmila

doi:10.1016/j.prp.2021.153393

Cited by 10 publications

(5 citation statements)

References 44 publications

(27 reference statements)

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“…MiR-27a-3p was selected in our work due to its negative correlation with ZNF268 expression. Various reports confirm that miR-27a-3p promotes proliferation and metastasis of renal cell carcinoma [ 35 , 36 ], consistently with our findings. Moreover, this work also provides supporting evidence on the ZNF268-regulating function of miR-27a-3p.…”

Section: Discussionsupporting

confidence: 93%

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration

Wang

et al. 2022

Bioengineered

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Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant kidney tumors with a poor prognosis. Accumulating evidence proves that zinc finger protein 268 (ZNF268) is associated with tumor progression, but the detailed regulatory functions of ZNF268 in ccRCC require further exploration. Thus, here we aim to characterize the role of ZNF268 in ccRCC. The clinical significance of ZNF268 was evaluated using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Subsequently, tumor-infiltrating immune cells, as well as upstream noncoding RNAs (ncRNAs) related to the tumor-suppressing function of ZNF268, were identified by in silico analyses. The expression of ZNF268 was significantly decreased in ccRCC samples compared with adjacent normal tissues. In addition, ZNF268 expression was negatively correlated with tumor progression and positively correlated with overall and disease-specific survival. TCGA and GTEx databases proved the potential tumor-suppressing function, which was measured both in vitro and in vivo after ZNF268 over-expression. Overexpression of ZNF268 effectively inhibited the proliferation, migration, invasion and promotied apoptosis of the Caki-1. The level of ZNF268 was positively related to the immune cell infiltration in the tumor. Moreover, we determined that the AC093157.1/miR-27a-3p axis can potentially regulate ZNF268 function in ccRCC. Our work describes a novel ncRNA-mediated ZNF268 function in ccRCC. ZNF268 acts as a tumor suppressor, and it is associated with apoptosis and immune cell infiltration in ccRCC.

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Section: Discussionsupporting

confidence: 93%

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration

Wang

et al. 2022

Bioengineered

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“…Previous studies demonstrated that a high CDH5 expression is mainly associated with tumor angiogenesis (20, 21). The aberrant expression of CDH5 in a variety of tumor tissues has been verified by bioinformatics analysis and experiments, and the results confirmed that high-expressed CDH5 was positively correlated with worse survival and higher tumor stage (33). Hendrix et al also reported that the down-regulation of CDH5 gene expression inhibits vasculogenic mimicry (20).…”

Section: Discussionmentioning

confidence: 72%

A comprehensive pan-cancer analysis of CDH5 in immunological response

Li,

Wu,

et al. 2023

Front. Immunol.

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BackgroundCadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor.MethodsThe clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8+ T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8+ T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5.ResultsThe expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of in vitro co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8+ T cells in TME of BCa.ConclusionIn summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint.

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“…We observed that miR-27a-3p might be a potential mediator between PEBP1P2 and PEBP1 via using miRDB and TargetScanHuman 7.1 databases, by which we found thatmiR-27a-3p can target both PEBP1P2 and PEBP1 mRNA. Furthermore,the overexpression of miR-27a-3p was observed in ccRCC tissues and associated with the oncogenic activity [21][22][23]. We further identified that miR-27a-3p directly targeted both PEBP1P2 and PEBP1 3'UTR using the luciferase report system and RNA-pulldown assays and demonstrated that PEBP1P2 regulated PEBP1 expression by acting as a ceRNA to absorb miR-27a-3p in ccRCC cells.…”

Section: Discussionmentioning

confidence: 79%

LncRNA PEBP1P2 Suppresses the Progression of Clear Cell Renal Cell Carcinoma Cells by Regulating the miR-27a-3p/PEBP1 Signal

Tang

et al. 2022

Preprint

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Background: Long noncoding RNA (lncRNA) PEBP1P2 has been shown to suppress the proliferation of vascular smooth muscle cells, but its role and underlying mechanisms in the development of clear cell renal cell carcinoma (ccRCC) remain largely unclear. Methods: Gene expression profiling interactive analysis (GEPIA) database was used to analyze the aberrant expression of lncRNAs in ccRCC tissues. Expression of RNAs and proteins was detected using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Ectopic expression of PEBP1P2 and miR-27a-3p was performed by pcDNA3.1 vector and miR-27a-3p mimics, respectively. Knockdown of PEBP1 mRNA was conducted by PEBP1 siRNA. Cell proliferation, migration, and invasion were analyzed using a CCK8 reagent and a trans-well assay, respectively. The sponge of PEBP1P2 to miR-27a-3p was investigated using Luciferase report system and RNA pull-down assays. Results: PEBP1P2 expression was decreased in ccRCC tissues compared with that in normal tissues and correlated with the size, TNM stage, and lymph node metastasis of the tumors, as well as the poor survival rates of ccRCC patients. Functionally, the enforced expression of PEBP1P2 inhibited the ability of ccRCC cells to proliferate, migrate, and invade in vitro . Mechanistically, PEBP1P2 suppressed the biological functions of ccRCC cells via increasing the mRNA and protein expression of PEBP1 and their expression had a positive correlation in ccRCC tissues. Furthermore, PEBP1P2 upregulated PEBP1 expression through acting as a competing endogenous RNA (ceRNA) to sponge miR-27a-3p, which directly target PEBP1 mRNA 3’UTR. Moreover, miR-27a-3p mimics rescued the decrease in the ability of ccRCC cells to proliferate, migrate, and invade mediated by PEBP1P2. Conclusion: Our findings indicated that PEBP1P2 suppressed ccRCC cell proliferation via regulating the miR-27a-3p/PEBP1 signal, suggesting that the PEBP1P2-miR-27a-3p/PEBP1 axis may be a potential therapeutic target for ccRCC.

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Inverse correlation of miR-27a-3p and CDH5 expression serves as a diagnostic biomarker of proliferation and metastasis of clear cell renal carcinoma

Cited by 10 publications

References 44 publications

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration

A comprehensive pan-cancer analysis of CDH5 in immunological response

LncRNA PEBP1P2 Suppresses the Progression of Clear Cell Renal Cell Carcinoma Cells by Regulating the miR-27a-3p/PEBP1 Signal

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