Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression

Santoni, Giorgio; Morelli, Maria Beatrice; Santoni, Matteo; Nabissi, Massimo; Marinelli, Oliviero; Amantini, Consuelo

doi:10.1007/978-3-030-12457-1_24

Cited by 16 publications

(12 citation statements)

References 69 publications

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“…In disagreement with us, Lu and colleagues found a negative influence of miR-211-5p on patients’ overall survival [ 10 ], even if the development of most melanomas has been specifically associated with the depletion of miR-211 transcript levels, thus supporting its positive effect [ 17 ]. In agreement with our results, Santoni and co-workers reported that the miR-211 expression is linked to tumor suppressor functions [ 29 ]. Furthermore, a direct connection has been shown between miR-211-5p and MITF , as it acts as a transcription factor for TRPM1 , which within its sixth intron encodes for miR211-5p [ 17 ].…”

Section: Discussionsupporting

confidence: 93%

“…In our cohort, similarly to miR-211-5p , MITF expression was also associated to longer melanoma-specific survival, findings that are supported by Mazar and colleagues [ 17 ]. Interestingly, TRPM1 was not directly linked to patients’ survival but to favorable pathological variables, such as Breslow’s depth and absence of ulceration, which is in line with other authors who defined TRPM1 loss as an excellent marker of melanoma aggressiveness [ 29 , 35 , 36 ]. Immune response molecules, namely CD2 and PD-L1 , were chosen in our study to define immune-type melanomas, which have been associated with improved patients’ survival [ 5 ].…”

Section: Discussionsupporting

confidence: 82%

“…Furthermore, in vitro studies have shown that miR-150-5p is downregulated by hypoxia in pancreatic cell lines [ 27 ]. Nevertheless, the above-mentioned miRNAs have been described as favorable biomarkers in skin melanomas or as tumor suppressor miRNAs [ 9 , 14 , 28 , 29 ]. The fact that different miRNAs have been detected in different geographical areas characterized by different altitudes supports the hypothesis for possible regulatory mechanisms induced by environmental conditions, such as a hypoxic environment and/or higher UVR exposure.…”

Section: Discussionmentioning

confidence: 99%

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The Association of Residential Altitude on the Molecular Profile and Survival of Melanoma: Results of an Interreg Study

Martino

Brunetti

Canzonieri

et al. 2020

Cancers

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Cutaneous melanoma (CM) incidence is rising worldwide and is the primary cause of death from skin disease in the Western world. Personal risk factors linked to environmental ultraviolet radiation (UVR) are well-known etiological factors contributing to its development. Nevertheless, UVR can contribute to the development of CM in different patterns and to varying degrees. The present study aimed at investigating whether altitude of residence can contribute to the development of specific types of CM and/or influence its progression. To this aim, 306 formalin-fixed and paraffin-embedded (FFPE) tissues from primary CM diagnosed in different geographical areas were submitted to B-RAF proto-oncogene serine/threonine kinase (BRAF) and N-RAS proto-oncogene GTPase (NRAS) mutational status detection and mRNA and miRNA profiling by qPCR. Genes were chosen for their functions in specific processes, such as immune response (CD2, PDL1, or CD274) and pigmentation (MITF, TYRP1, and TRPM1). Furthermore, four microRNAs, namely miR-150-5p, miR-155-5p, miR-204-5p, and miR-211-5p, were included in the profiling. Our results highlight differences in the gene expression profile of primary CM with respect to the geographical area and the altitude of residence. Melanoma-specific survival was influenced by the gene expression of mRNA and miRNAs and varied with the altitude of patients’ residence. In detail, TYRP1 and miR-204-5p were highly expressed in patients living at higher altitudes, unlike miR-150-5p, miR-155-5p, and miR-211-5p. Since miRNAs are highly regulated by reactive oxygen species, it is possible that different regulatory mechanisms characterize CMs at different altitudes due to the different environment and UVR intensity.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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The Association of Residential Altitude on the Molecular Profile and Survival of Melanoma: Results of an Interreg Study

Martino

Brunetti

Canzonieri

et al. 2020

Cancers

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“…3 As the major Ca 2+ influx mechanism, transient receptor potential (TRP) channels form a superfamily of non-selective cation channels with varying degrees of Ca 2+ permeability that respond to a variety of distinct stimuli, including chemicals, temperature and mechanical stress. 21 The de-regulation of TRP channels can stimulate RCC development and progression, 22 such as TRPM3, 23,24 TRPC6 25 and TRPC1. Among TRP family channels, TRPV5 is remarkably calcium-selective channels which serve as calcium entry mechanisms in kidney.…”

Section: Discussionmentioning

confidence: 99%

<p>Modulation of Calcium Homeostasis May Be Associated with Susceptibility to Renal Cell Carcinoma in Diabetic Nephropathy Rats</p>

Luo

Waaga-Gasser

et al. 2020

CMAR

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Introduction: Clinical studies have indicated a relationship between diabetic nephropathy (DN) and the incidence and prevalence of renal cell carcinoma (RCC). However, the mechanism linking diabetic nephropathy and renal cell carcinoma has not yet to be identified. Methods: In this study, a total of 42 male Sprague Dawley (SD) rats were randomly assigned to a DN group (n=35) and a control group (n=7). All animals in the DN group were unilaterally nephrectomized and treated with streptozotocin with the development of blood glucose levels >16.7mmol/L and dominant proteinuria and were compared to controls without such changes. Histopathologic alterations in the kidneys were examined by HE staining and Ki-67 immunohistochemistry. Differentially expressed genes were identified and validated by RNA-seq and PCR. Results: As the results, except for two rats that failed to develop the DN model and were excluded from the analysis, 33 rats in the DN group with overt signs of DN demonstrated significantly higher food and water intake, urine production, and urine protein and urinary protein/creatinine ratio than controls. Overall, 15.2% (n=5/33) of DN animals developed RCC while none tumors were observed in the control group (n=0/7). RNA-seq analysis in these animals indicated different TRPV5 gene expression and calcium pathway expression in DN animals with developing tumors, when compared with animals with no obvious tumors. In addition, DN animals diagnosed with RCC showed increased expression of GLUT2 and c-met, when compared to controls and DN animals without tumors. Discussion: In conclusion, the disordered calcium metabolism, especially disturbed TRPV5 mediated Ca 2+ signal, may have been related to the development of RCC in DN rats. Further studies related to the detailed mechanism are still needed.

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“…pivotal regulators of gene expression by directly binding to the 3′-untranslated region (UTR) of the targeted genes [4]. MicroRNAs have been reported to be involved in a variety of cellular processes, including differentiation, proliferation, apoptosis, invasion and migration [5,6]. Dysregulated miRNAs have been correlated with tumorigenesis, cancer progression and response to therapy with a role that activates or silences some oncogenes or tumor suppressors in human [7,8].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma

Dai

Zhang

et al. 2020

Cancer Cell Int

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Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal human malignancy, and previous researches support the contribution of microRNA (miRNA) to cancer progression. MiR-122-5p is reported to participate in the regulation of various cancers, while the function of miR-122-5p in PDAC remains unclear. In this study, we investigated the precise mechanism of miR-122-5p involved in PDAC pathogenesis. Methods: The expression levels of miR-122-5p were detected in human PDAC tissues and cell lines by miRNA RT-PCR. The effects of miR-122-5p on cell proliferation were explored by MTT assays, colony formation assays and flow cytometry assays. The ability of migration and invasion was determined by transwell assays. Dual Luciferase reporter assay was performed to validate the direct interaction between miR-122-5p and its target gene. The related molecules of cell cycle, apoptosis and epithelial-mesenchymal transition (EMT) were examined with qRT-PCR and western blot. In addition, xenograft mouse models were applied to explore the effects of miR-122-5p in vivo. Results: MiR-122-5p was underexpressed, while CCNG1 was highly expressed in PDAC tissues and cells. MiR-122-5p was negatively correlated with TNM stage, tumor size and lymph node metastasis in PDAC patients. Overexpression of miR-122-5p suppressed the proliferation, migration and invasion in vitro and inhibited tumorigenesis in vivo. Furthermore, CCNG1 was a direct target of miR-122-5p. Upregulated CCNG1 could partially reverse the effects caused by miR-122-5p. Moreover, miR-122-5p inhibited EMT through downregulation of CCNG1. Conclusion: Overexpression of miR-122-5p could inhibit cell proliferation, migration, invasion, and EMT by downregulating CCNG1 in PDAC, suggesting a potential therapeutic target for PDAC.

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Targeting Transient Receptor Potential Channels by MicroRNAs Drives Tumor Development and Progression

Cited by 16 publications

References 69 publications

The Association of Residential Altitude on the Molecular Profile and Survival of Melanoma: Results of an Interreg Study

The Association of Residential Altitude on the Molecular Profile and Survival of Melanoma: Results of an Interreg Study

<p>Modulation of Calcium Homeostasis May Be Associated with Susceptibility to Renal Cell Carcinoma in Diabetic Nephropathy Rats</p>

MicroRNA-122-5p inhibits cell proliferation, migration and invasion by targeting CCNG1 in pancreatic ductal adenocarcinoma

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