Urine microRNAs as potential noninvasive biomarkers in urologic cancers

Renal cell carcinoma (RCC) is the most common cancer of the kidney and accounts for 2-3% of all adult malignancies. Clear cell carcinoma represents the most common histologic subtype, while papillary Renal Cell Carcinoma (pRCC) accounts for 10-20% of all renal cell cancers. While the inactivation of VHL gene can be found in the majority of clear cell carcinomas, different molecular mechanisms are involved into pRCC biology. Mutations in the MET oncogene are an essential step into the pathogenesis of hereditary pRCC forms, but they can be found only in a small rate of sporadic cases. Several agents, including anti-VEGF drugs and mTOR inhibitors, are possible options in the treatment of advanced and metastatic pRCC, following the demonstration of efficacy obtained in clinical trials including all RCC histologic subtypes. However, data specifically obtained in the subgroup of patients affected by pRCC are limited and not conclusive. Several ongoing trials are evaluating the efficacy of targeted therapy in papillary form. However, more rationale approaches based on molecular studies would help improving the outcome of these patients. Among others, MET inhibitors and targeted immunotherapy are promising new strategies for hereditary and sporadic disease. This review summarizes current knowledge on pRCC tumorigenesis and discusses recent and ongoing clinical trials with new therapeutic agents.

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“…Analysis of urinary miRNAs indicate a potential new approach for diagnosis and follow-up of urologic cancers [53].…”

Section: Micrornasmentioning

confidence: 99%

Papillary renal cell carcinoma: A review of the current therapeutic landscape

Courthod

Tucci

Maïo

et al. 2015

Critical Reviews in Oncology/Hematology

116

130

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“…Depending on the type of cancer different body fluids have been used for analysis (Figure 1). For instance, blood-based samples are usually used for hematological malignancies and many solid tumors [43, 159], such as breast, prostate, and lung cancer, while urine can be used for urological cancers [188], saliva for oral cancers [189], and cerebrospinal fluid for brain cancers [190]. …”

Section: Secretion and Uptake Of Cell-free Mirnasmentioning

confidence: 99%

Regulation of cancer metastasis by cell-free miRNAs

Alečković

Kang

2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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MicroRNAs (miRNAs) are integral molecules in the regulation of numerous physiological cellular processes that have emerged as critical players in cancer initiation and metastatic progression, both by promoting and suppressing metastasis. Recently, cell-free miRNAs shed from cancer cells into circulation have been reported in cancer patients, raising hope for development of novel biomarkers that can be routinely measured in easily accessible samples. In fact, establishing miRNA expression in the circulation likely has advantages over determination in primary tumor tissue, further augmenting the potential applications of miRNA detection in oncological practice. In addition, secretion of miRNAs impacting distant cell signaling or promoting the formation of a niche that sustains a distant tumor microenvironment allows for new treatment approaches to thwart cancer progression.

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“…miRs were frequently altered in most urologic cancers, playing significant roles as oncogenes or tumor suppressors, and miRs also target common pathways involved in the regulation of cell growth, proliferation, invasion, and apoptosis in bladder carcinogenesis 10,12,13. It has been suggested that miR-125b targets E2F transcription factor 3 ( E2F3 ) and that miR-125b may be involved in the regulation of the G1/S transition via the E2F3 -cyclin A2 signaling pathway in bladder cancer 14.…”

Section: Introductionmentioning

confidence: 99%

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

Xiao

Lin²,

Zhu

et al. 2016

OTT

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ObjectiveTo assess whether microRNA-126 (miR-126) targets phosphatidylinositol 3-kinase regulatory subunit beta (PIK3R2) and to determine the potential roles of miR-126 in regulating proliferation and invasion via the PIK3R2-mediated phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signaling pathway in the human bladder BLS cell line.Materials and methodsA recombinant lentivirus (Lv) vector expressing miR-216 (Lv-miR-126) was successfully constructed, and Lv-miR-126 and Lv vector were transfected into the BLS cell line. A direct regulatory relationship between miR-126 and the PIK3R2 gene was demonstrated by luciferase reporter assays. To determine whether PIK3R2 directly participates in the miR-126-induced effects in BLS cells, anti-miR-126 and a PIK3R2 small interfering RNA (siRNA) were transfected into the BLS cells. Quantitative real-time polymerase chain reaction was used to measure miR-126 and PIK3R2 expressions. 5-Ethynyl-2′-deoxyuridine and colony formation assays to assess cell proliferation, flow cytometry for cell apoptosis and cell cycle analysis, Transwell assays for cell migration and invasion, and Western blots for PIK3R2, PI3K, phosphorylated PI3K (p-PI3K), Akt, and phosphorylated Akt (p-Akt) protein expressions were performed.ResultsLv-miR-126 significantly enhanced the relative expression of miR-126 in the BLS cells after infection (P<0.0001). MiR-126 overexpression inhibited the proliferation, cloning, migration, and invasion of BLS cells, promoted cell apoptosis, and induced S phase arrest (all P<0.05). PIK3R2, p-PI3K, and p-Akt protein expressions were significantly decreased in the BLS cells infected with Lv-miR-126. Luciferase assays showed that miR-126 significantly inhibited the PIK3R2 3′ untranslated region (3′UTR) luciferase reporter activity (P<0.05). The anti-miR-126 + PIK3R2 siRNA group had significantly decreased PIK3R2, p-PI3K, and p-Akt expressions compared with those of anti-miR-126 alone, as well as significantly decreased proliferation, invasion, and metastasis and increased apoptosis compared with the anti-miR-126 group (all P<0.05). Additionally, proliferation, invasion, and metastasis were significantly increased, and cell apoptosis was decreased compared with the PIK3R2 siRNA group (all P<0.05).ConclusionOverexpression of miR-126 negatively regulated the target gene PIK3R2 and further inhibited the PI3K/Akt signaling pathway, thereby inhibiting proliferation, migration, and invasion and promoting apoptosis in BLS cells.

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Urine microRNAs as potential noninvasive biomarkers in urologic cancers

Cited by 91 publications

References 40 publications

Papillary renal cell carcinoma: A review of the current therapeutic landscape

Papillary renal cell carcinoma: A review of the current therapeutic landscape

Regulation of cancer metastasis by cell-free miRNAs

MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the <em>PIK3R2</em>-mediated PI3K/Akt signaling pathway

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