MicroRNA profile in stage I clear cell renal cell carcinoma predicts progression to metastatic disease

Moynihan, Matthew; Sullivan, Travis; Burks, Eric; Schober, Jared P.; Calabrese, Marc; Fredrick, Ariel; Kalantzakos, Thomas; Warrick, Joshua I.; Canes, David; Raman, Jay D.; Rieger-Christ, Kimberly

doi:10.1016/j.urolonc.2020.05.006

Cited by 10 publications

(16 citation statements)

References 61 publications

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“…miRNA expression profiles have also been demonstrated to be capable of identifying ccRCC patients with a higher risk of relapse following nephrectomy [11]. In ccRCC patients with pT1 ccRCC tumors, we identified miR-424-5p, among others, as downregulated in those that progressed to metastatic disease [9].…”

Section: Introductionmentioning

confidence: 81%

“…The prognostic capability of miRNAs has been investigated in numerous studies, with their impact driven through altered protein expression of tumor suppressors and oncogenes. Our previous study identified miR-424-5p, among others, as downregulated in small stage I ccRCC tumors that would later progress to metastatic disease [9]. This study investigated the impact and interaction of miR-424-5p and OGT on the proliferation, migration, and invasion of ccRCC cells.…”

Section: Discussionmentioning

confidence: 97%

“…One area of particular interest for identifying novel prognostic factors is within pathologic stage I (pT1, N0, Mx) ccRCC. While these tumors routinely yield favorable outcomes for the patient, cited in the 81-92% range [9], a small subset of these individuals will progress to metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

“…A previous study from our laboratory further investigated this phenomenon by identifying miRNAs as potential biomarkers in identifying pT1 tumors that would progress to metastatic disease [9]. miRNAs are small, non-coding RNA molecules of about 20 nucleotides in length that post-transcriptionally bind to the 3 UTR of mRNA transcripts to suppress gene expression.…”

Section: Introductionmentioning

confidence: 99%

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MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

Kalantzakos

Sullivan

Gloria

et al. 2021

Cancers

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MicroRNAs (miRNAs) are non-coding post-transcriptional regulators of gene expression that are dysregulated in clear cell renal cell carcinoma (ccRCC) and play an important role in tumor progression. Our prior work identified a subset of miRNAs in pT1 ccRCC tumors, including miR-424-5p, that are associated with an aggressive phenotype. We investigate the impact of this dysregulated miRNA and its protein target O-GlcNAc-transferase (OGT) to better understand the mechanisms behind aggressive stage I ccRCC. The ccRCC cell lines 786-O and Caki-1 were used to assess the impact of miR-424-5p and OGT. Cells were transfected with pre-miR-424-5p, a lentiviral anti-OGT shRNA, or were treated with the demethylating agent 5-Aza-2′-deoxycytidine. Cell proliferation was measured via MT cell viability assay. Cell migration and invasion were analyzed using Transwell assays. The expression of miR-424-5p was determined through qRT-PCR, while OGT protein expression was evaluated through Western blotting. The interaction between miR-424-5p and OGT was confirmed via luciferase reporter assay. The transfection of ccRCC cells with pre-miR-424-5p or anti-OGT shRNA significantly inhibited cell proliferation, migration, and OGT expression, while miR-424-5p also attenuated cell invasion. Addition of the demethylating agent significantly reduced cell proliferation, migration, invasion, and OGT expression, while significantly increasing the expression of miR-424-5p. Altogether, these findings suggest that epigenetic downregulation of miR-424-5p, which in turn augments OGT expression, contributes to the creation of aggressive forms of stage I ccRCC.

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Section: Introductionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

Kalantzakos

Sullivan

Gloria

et al. 2021

Cancers

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“…Similarly, many studies have reported the relationship between miRNAs and circRNAs in breast cancer (17)(18)(19). Previous work has demonstrated that miR-145-5p regulates the proliferation of pulmonary microvascular endothelial cells (20), renal cell carcinoma cells (21), ovarian cancer cells (22), non-small cell lung cancer cells(NSCLC) (16), and breast cancercells (23). Notably, the complementary sites between miR-145-5p and circRNA DENND4C were predicted by a bioinformatics analysis using starBase.…”

Section: Introductionmentioning

confidence: 96%

The circRNA DENND4C/miR-145-5p/HOXA9 Pathway Regulates Tumor Growth and Bone Metastasis in Breast Cancer

Zhu

Lian

Chen

et al. 2020

Preprint

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BackgroundCircular RNAs (circRNAs) are involved in the occurrence and development of breast cancer bone metastasis. This study aims to identify whether the circRNA DENND4C/ miR145-5p/HOXA9 axis is involved in the regulation of cell invasion and migration and breast cancer progression.MethodscircRNA DENND4C, miR-145-5p and HOXA9 expression was measured in serum samples from healthy volunteers, breast cancer patients without bone metastasis and breast cancer patients with bone metastasis. Moreover, we analyzed the levels of circRNA DENND4C, miR‑145-5p and HOXA9 according to different conditions of differentiation, tumor volume and lymph node metastasis. The online software starBases and the dual-luciferase reporter gene assay were used to predict the relationship miR-145-5p, circRNA DENND4C and HOXA9 mRNA. MTT assays were performed to assess the effect of circRNA DENND4C on proliferation. To assess the proliferation of breast cancer cells among different groups. Statistical significance was determined byStudent's t‑test which was used for comparisons between two groups and one‑way analysis of variance followed by Tukey's post hoc test for comparisons between more than two groups.ResultsThe expression patterns of circRNA DENND4C, miR145-5p and HOXA9 were altered in patients with breast cancer bone metastasis. Notably, the stimulatory effects of circRNA DENND4C overexpression on HOXA9 were eliminated by miR-145-5p upregulation. circRNA DENND4C overexpression promotes proliferation, migration and invasiveness by regulating the miR-145-5p/HOXA9 axis. circRNA DENND4C downregulation suppresses proliferation, cell viability and invasiveness by regulating the miR-145-5p/HOXA9 axis. ConclusionOur study suggest that circRNA DENND4C/miR-145-5p/HOXA9 pathway was involved in tumor growth and bone metastasis in breast cancer. This findings may facilitate the development of potential therapeutic agents to improve the prognosis of patients with breast cancer bone metastasis.

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Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma

Wang

Shen²,

Mo³

et al. 2022

Translational Oncology

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MicroRNA profile in stage I clear cell renal cell carcinoma predicts progression to metastatic disease

Cited by 10 publications

References 61 publications

MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

MiRNA-424-5p Suppresses Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma and Attenuates Expression of O-GlcNAc-Transferase

The circRNA DENND4C/miR-145-5p/HOXA9 Pathway Regulates Tumor Growth and Bone Metastasis in Breast Cancer

Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma

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