Construction of five microRNAs prognostic markers and a prognostic model for clear cell renal cell carcinoma

Zhou, Qi; Zhang, Zhiyu; Ang, Xiaojie; Hu, Can; Ouyang, Jun

doi:10.21037/tcr-21-37

Cited by 3 publications

(5 citation statements)

References 40 publications

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“…Levels of this miRNA were found to be higher in sunitinib resistant cells when compared with parental ones [45]. In agreement with our results, the work of Zhou et al, using the TCGA database, showed that high expression levels of miR-130b in renal tumour samples were related to worse survival [46]. We also demonstrated that down-regulation of FLT1, PRDM1 and SAV1 were significantly associated with non-responsive ccRCC patients.…”

Section: Discussionsupporting

confidence: 92%

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients

Armesto,

Nemours,

Arestín

et al. 2024

IJMS

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Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20–30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.

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Section: Discussionsupporting

confidence: 92%

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients

Armesto,

Nemours,

Arestín

et al. 2024

IJMS

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“…MiR-155-5p has also been demonstrated to mediate characteristics of ccRCC progression such as proliferation, migration, and invasion [13,44,45]. Furthermore, other studies have examined the utility of miR-155-5p as a biomarker for prognostic outcomes in those with ccRCC [48,49]. Beyond prognosis, a recent paper by Sequeira et al 2022 found that miR-155-5p aided in accurate detection of RCC from patient plasma [50].…”

Section: Discussionmentioning

confidence: 99%

“…Cells were seeded into 35 mm dishes (Corning Costar Corporation, Cambridge, MA, USA) in duplicate at a density of 2 × 10 4 cells/mL, determined using a hemocytometer (American Optical Corporation, Buffalo, NY, USA). Forty-eight [48] hours after culturing, RealTime-Glo™ MT Cell Viability Assay (Promega, Madison, WI, USA) reagents were added to each dish at a 1:2000 dilution. Luminescence readings were obtained utilizing the GloMax ® 20/20 Luminometer (Promega, Madison, WI, USA) 1 h after the addition of the Cell Viability reagents.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

MicroRNA-155-5p Targets JADE-1, Promoting Proliferation, Migration, and Invasion in Clear Cell Renal Cell Carcinoma Cells

Kalantzakos

Hooper

Das

et al. 2023

IJMS

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Clear cell renal cell carcinoma (ccRCC) incidence has been rising in recent years, with strong association between differential microRNA (miRNA) expression and neoplastic progression. Specifically, overexpression of miR-155-5p has been associated with promoting aggressive cancer in ccRCC and other cancers. In this study, we further investigate the role of this miRNA and one of its protein targets, Jade-1, to better understand the mechanism behind aggressive forms of ccRCC. Jade-1, a tumor suppressor, is stabilized by Von-Hippel Lindau (VHL), which is frequently mutated in ccRCC. Experiments featuring downregulation of miR-155-5p in two ccRCC cell lines (786-O and Caki-1) attenuated their oncogenic potential and led to increased levels of Jade-1. Conversely, knockdown experiments with an anti-Jade-1 shRNA in 786-O and Caki-1 cells showed increased metastatic potential through elevated proliferation, migration, and invasion rates. In a mouse xenograft model, downregulation of miR-155 decreased the rate of tumor implantation and proliferation. Direct interaction between miR-155-5p and Jade-1 was confirmed through a 3′UTR luciferase reporter assay. These findings further elucidate the mechanism of action of miR-155-5p in driving an aggressive phenotype in ccRCC through its role in regulating Jade-1.

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“…The function of miR-1251-5p is the only establishment. In ovarian cancer cells, by addressing the tumor suppressor TBCC, Zhou et al [ 8 ] found that miR-1251-5p increased carcinogenesis and autophagy. However, it is unknown if miR-1251-5p performs a function in developing HCC [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…miR-1251-5p was found on chromosome 12q23.1, but there were few studies about this miRNA in ccRCC. Liang et al [ 7 ] and Zhou et al [ 8 ] have confirmed that miR-1251-5p is a prognostic factor of ccRCC based on database analysis, but no experimental verification has been carried out and only TCGA database has been used for analysis. The activity of miR-1251-5p is upregulated with hepatocellular carcinoma cells, according to a microarray study of miRNAs, and could represent a viable therapeutic target for therapy [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

miR-1251-5p Overexpression Inhibits Proliferation, Migration, and Immune Escape in Clear Cell Renal Cell Carcinoma by Targeting NPTX2

Yue

Lin

Yuan

et al. 2022

Journal of Oncology

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Background. miR-1251-5p was identified as a tumor suppressor in a variety of malignancies; however, its biological function in clear cell renal cell carcinoma (ccRCC) is unknown. Methods. The Cancer Genome Atlas (TCGA) database was used to download expression information, including miR-1251-5p, in 521 ccRCC tissues and 71 ordinary tissues, and bioinformatics was used to explore possible target mRNAs. The relationship between miR-1251-5p, target mRNA activity, and clinical factors was examined. To estimate the biological activity of miR-1251-5p and target mRNA in ccRCC cells, we used MTT, colony formation, enzyme-linked immunosorbent, and Transwell assays. We employed a dual-luciferase reporter assay and a western blot to examine the molecular mechanisms of miR-1251-5p in ccRCC cells. In addition, the expressions of miR-1251-5p and target mRNA were further verified in the GEO database. Results. Our findings revealed that miR-1251-5p binds with NPTX2’s 3′-UTR. In TCGA and GEO datasets, miR-1251-5p activity is found to be lower in ccRCC tissues than that in nearby conventional tissues, although NPTX2 activity is higher. In ccRCC sufferers, miR-1251-5p and NPTX2 act as biomarkers that indicate a bad prognosis. Meanwhile, in miR-1251-5p tissues, NPTX2 expression and multiple clinical variables (survival status, grade, T staging, N staging, M staging, and clinical stage) had significant differences p < 0.05 . Structurally, miR-1251-5p inhibited proliferation, migration, and immune escape of ccRCC cells by targeting NPTX2. Conclusion. Our findings indicate that miR-1251-5p constrained ccRCC cell advancement, migration, and immune evasion via targeting NPTX2, providing novel insights into ccRCC target treatment.

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Construction of five microRNAs prognostic markers and a prognostic model for clear cell renal cell carcinoma

Cited by 3 publications

References 40 publications

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients

Identification of miRNAs and Their Target Genes Associated with Sunitinib Resistance in Clear Cell Renal Cell Carcinoma Patients

MicroRNA-155-5p Targets JADE-1, Promoting Proliferation, Migration, and Invasion in Clear Cell Renal Cell Carcinoma Cells

miR-1251-5p Overexpression Inhibits Proliferation, Migration, and Immune Escape in Clear Cell Renal Cell Carcinoma by Targeting NPTX2

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