miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

Jin, Lü; Zeng, Zhen; Li, Yifan; He, Tao; Hu, Jia; Lü, Jiaju; Chen, Mingwei; Gui, Yaoting; Chen, Yun; Lai, Yongqing

doi:10.3892/ol.2017.5985

Cited by 15 publications

(6 citation statements)

References 37 publications

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“…However, our data on the frequent hypermethylation of the MIR-125b-1 gene and the hypermethylation linkages with progression and metastasis (Varachev et al, 2018) do not agree with the increased level of this miRNA and its role in promoting cell (Jin et al, 2017). The properties of this miRNA are also ambiguous in other types of cancer, such as breast cancer (Loginov et al, 2018a).…”

Section: Aberrantly Methylated Mirna Genes In Ccrccmentioning

confidence: 56%

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

et al. 2019

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Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search for new biomarkers. Epigenetic regulatory mechanisms, such as genome-wide DNA methylation and inhibition of protein translation by interaction of microRNA (miRNA) with its target messenger RNA (mRNA), are deeply involved in the pathogenesis of human cancers, including ccRCC, and may be used in its diagnosis and prognosis. Here, we review oncogenic and oncosuppressive miRNAs, their putative target genes, and the crucial pathways they are involved in. The contradictory behavior of a number of miRNAs, such as suppressive and anti-metastatic miRNAs with oncogenic potential (for example, miR-99a, miR-106a, miR-125b, miR-144, miR-203, miR-378), is examined. miRNAs that contribute mostly to important pathways and processes in ccRCC, for instance, PI3K/AKT/mTOR, Wnt-β, histone modification, and chromatin remodeling, are discussed in detail. We also separately consider their participation in crucial oncogenic processes, such as hypoxia and angiogenesis, metastasis, and epithelial-mesenchymal transition (EMT). The review also considers the interactions of long non-coding RNAs (lncRNAs) and miRNAs of significance in ccRCC. Recent advances in the understanding of the role of hypermethylated miRNA genes in ccRCC and their usefulness as biomarkers are reviewed based on our own data and those available in the literature. Finally, new data and perspectives concerning the clinical applications of miRNAs in the diagnosis, prognosis, and treatment of ccRCC are discussed.

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Section: Aberrantly Methylated Mirna Genes In Ccrccmentioning

confidence: 56%

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

et al. 2019

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“…miR-495 was previously described to suppress cell proliferation and migration in RCC [44] and epigenetic regulation of miR-495 was linked to tumor suppression in breast cancer [45]. Moreover, posttranscriptional regulation of TACSTD2 expression by miR-125b as well as promotion of cell migration in RCC has been reported previously [46,47]. Also, functional in vitro and in vivo analyses for TACSTD2 in other human tumor entities like lung adenocarcinoma, HCC and cholangiocarcinoma, consistently demonstrated that silencing of TACSTD2 gene expression results in a significant increase of tumor growth [34] and leads to cell proliferation and migration [33,35].…”

Section: Discussionmentioning

confidence: 90%

DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers

et al. 2021

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Background DNA methylation is frequently observed in the development and progression of many human tumors as well as renal cell cancer (RCC). Tumor Associated Calcium Signal Transducer 2 (TACSTD2) participates in cell cycle progression through MAPK signalling pathway activation. Moreover, tumor-specific hypermethylation and association with aggressive cancer characteristics has been found for lung adenocarcinoma, hepatocellular carcinoma and cholangiocarcinoma. Whether TACSTD2 is tumor specifically hypermethylated in RCC or shows association of methylation with adverse clinicopathological parameters and survival of patients has not been investigated at yet. Methods Quantitative methylation-specific PCR (qMSP) analysis of a locus in the intron 1 region of TACSTD2 gene was carried out in a cross-sectional study of 127 paired RCC and normal samples. In silico analysis of TACSTD2 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset of 280 patients served as validation cohort. Statistical analyses were carried out using the two-sided paired t-test for matched tumor and normal sample comparisons, logistic regression for subgroup comparisons, Cox regression for analysis of recurrence free survival (RFS) and Pearson correlation analysis for correlation of TACSTD2 methylation and TACSTD2 mRNA in KIRC data. Results Higher methylation levels in RCC were significantly associated with advanced disease (p < 0.001), high tumor stage (p = 0.003), tumor differentiation (p = 0.033) and presence of lymph node (p = 0.021) or distant metastases (p = 0.008). TACSTD2 hypermethylation was associated with a shorter RFS of patients and demonstrate statistical independency from clinical parameters as state of metastasis, tumor stage, grade and state of advanced disease. In silico validation using TCGA KIRC data also demonstrated association of TACSTD2 loci with adverse clinicopathology and shortened RFS of patients. In addition, in silico analyses of TCGA KIRC data showed an inverse correlation between DNA methylation levels of TACSTD2 and mRNA expression. Conclusions Our results suggest an association between TACSTD2 methylation and disease progression and clinical course of RCC.

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“…At present, some studies have suggested that a lot of miRNAs could act as oncogenic miRNAs or tumor suppressor miRNAs to participate in the tumorigenesis and progressions of ccRCC, and they might serve as diagnosic and prognosic biomarkers for ccRCC patients [21][22][23][24]. However, several studies have shown that some miRNAs may play complete contradictor roles in diagnosic and prognosic effects for ccRCC, such as miR-99a [25,26], miR-106a [27,28], miR-125b [21,29], miR-144 [30,31], miR-203 [32,33], and miR-378 [34,35], which might greatly limit their applications into the clinical diagnosis and prognosis for ccRCC patients. Therefore, we should further study the functional roles of miRNAs as potentially diagnostic and prognostic biomarkers for ccRCC, whilst it is also very necessary for expanding the screening of new reliable miRNAs as diagnostic and prognostic biomarkers for ccRCC.…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor and miRNA Interplays Can Manifest the Survival of ccRCC Patients

Qin

Shi

Wang

et al. 2019

Cancers

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Clear cell renal cell carcinoma (ccRCC) still remains a higher mortality rate in worldwide. Obtaining promising biomakers is very crucial for improving the diagnosis and prognosis of ccRCC patients. Herein, we firstly identified eight potentially prognostic miRNAs (hsa-miR-144-5p, hsa-miR-223-3p, hsa-miR-365b-3p, hsa-miR-3613-5p, hsa-miR-9-5p, hsa-miR-183-5p, hsa-miR-335-3p, hsa-miR-1269a). Secondly, we found that a signature containing these eight miRNAs showed obviously superior to a single miRNA in the prognostic effect and credibility for predicting the survival of ccRCC patients. Thirdly, we discovered that twenty-two transcription factors (TFs) interact with these eight miRNAs, and a signature combining nine TFs (TFAP2A, KLF5, IRF1, RUNX1, RARA, GATA3, IKZF1, POU2F2, and FOXM1) could promote the prognosis of ccRCC patients. Finally, we further identified eleven genes (hsa-miR-365b-3p, hsa-miR-223-3p, hsa-miR-1269a, hsa-miR-144-5p, hsa-miR-183-5p, hsa-miR-335-3p, TFAP2A, KLF5, IRF1, MYC, IKZF1) that could combine as a signature to improve the prognosis effect of ccRCC patients, which distinctly outperformed the eight-miRNA signature and the nine-TF signature. Overall, we identified several new prognosis factors for ccRCC, and revealed a potential mechanism that TFs and miRNAs interplay cooperatively or oppositely regulate a certain number of tumor suppressors, driver genes, and oncogenes to facilitate the survival of ccRCC patients.

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miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

Cited by 15 publications

References 37 publications

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

DNA methylation of tumor associated calcium signal transducer 2 (TACSTD2) loci shows association with clinically aggressive renal cell cancers

Transcription Factor and miRNA Interplays Can Manifest the Survival of ccRCC Patients

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