MicroRNA 15a, Inversely Correlated to PKCα, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples

Brandenstein, Melanie von; Pandarakalam, Jency J.; Kroon, L. de; Löser, Heike; Herden, Jan; Braun, Gabriele; Wendland, Katherina; Dienes, Hans Peter; Engelmann, U.; Fries, Jochen W.U.

doi:10.1016/j.ajpath.2012.01.014

Cited by 105 publications

(102 citation statements)

References 37 publications

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“…We observed an initial upregulation and a subsequent downregulation of miR-15a in the metastatic samples, albeit at levels above those detected in normal tissue. In two studies, an increase of miR-15a was found to be of negative predictive value in renal cell carcinoma (52) or diffuse large B-cell lymphoma (53). There are now large numbers of studies that established miRNA profiles of prostate carcinoma, which, to some extent, report conflicting results (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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MicroRNAs (miRNA) posttranscriptionally regulate gene expression and are important in tumorigenesis. Previous deep sequencing identified the miRNA profile of prostate carcinoma versus nonmalignant prostate tissue. Here, we generated miRNA expression profiles of prostate carcinoma by deep sequencing, with increasing tumor stage relative to corresponding nonmalignant and healthy prostate tissue, and detected clearly changed miRNA expression patterns. The miRNA profiles of the healthy and nonmalignant tissues were consistent with our previous findings, indicating a high fidelity of the method employed. In the tumors, quantitative real-time PCR (qRT-PCR) analysis of 40 paired samples of prostate carcinoma versus normal tissue revealed significant upregulation of miR-20a, miR-148a, miR-200b, and miR-375 and downregulation of miR-143 and miR-145. Hereby, miR-375 increased from normal to organ-confined tumors (pT2 pN0), slightly decreased in tumors with extracapsular growth (pT3 pN0), but was then expressed again at higher levels in lymph node metastasizing (pN1) tumors. The sequencing data for miR-375 were confirmed by Northern blotting and qRT-PCR. The regulation for other selected miRNAs could, however, not be confirmed by qRT-PCR in individual tumor stages. MiR-200b, in addition to miR-200c and miR-375 reduced the expression of SEC23A. Interestingly, miR-375, found by sequencing in pT2 upregulated by us and others in tumor versus normal tissue, and miR-15a, found by sequencing in pT2 and pT3 and in the metastasizing tumors, target the phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate members of the AKT family of signal transducers, thereby inhibiting cell growth. Coexpression of miR-15a and miR-375 resulted in downregulation of PHLPP1/2 and strongly increased prostate carcinoma cell growth.Implications: These genomic data reveal relevant miRNAs in prostate cancer that may have biomarker and therapeutic potential. Mol Cancer Res; 12(2); 250-63. Ó2013 AACR. IntroductionProstate carcinoma is the second most frequently diagnosed malignancy and a leading cause of cancer-related death in men worldwide (1). The underlying mechanisms resulting in invasive growth after dissemination of the primary tumor from the initial site in the prostate are not completely understood. MicroRNAs (miRNAs) are now recognized as contributing factors to the induction, growth, and metastasis

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Section: Discussionmentioning

confidence: 99%

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Hart

Nolte

Wach

et al. 2014

Molecular Cancer Research

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“…Different types of RCC show significantly different patterns in the expression of PKC isozymes. PKC I, II, , and are expressed in RCCs, while PKC , I, II, , and are found in oncocytoma, the most common benign solid renal tumor [473]. Moreover, PKC , I, II, , , , , , and have been detected in the human RCC cell line CCF-RC1 [474].…”

Section: Renal Cell Carcinoma (Kidney Cancer)mentioning

confidence: 99%

Protein Kinase C (PKC) Isozymes and Cancer

Kang

2014

New Journal of Science

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Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

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“…[65][66][67][68][69][70][71][72][73][74][75][76] Specifically, relatively few studies, including only one multicentre study 67 , have been conducted, and most studies did not perform an internal validation with a training and validation set or even an internal validation approach, such as bootstrapping or cross-validation. Moreover, all studies except one used serum as the source of RNA despite plasma being the blood component of choice since the release of miRNAs from blood cells such as the miRNA-enriched platelets into serum occurs during the coagulation process.…”

Section: [H1] Biofluid Mirnas In Kidney Cancermentioning

confidence: 99%

“…Surprisingly, only one study using urine samples for miRNA analyses in patients with RCC has been reported. Von Brandenstein et al 65 measured miR-15a levels in whole-urine samples from patients with ccRCC. Distinctly higher concentrations were observed in ccRCC patients than in the urine of patients with benign renal oncocytoma, urinary bladder cancer or other, nonurological tumours.…”

Section: [H1] Biofluid Mirnas In Kidney Cancermentioning

confidence: 99%

The translational potential of microRNAs as biofluid markers of urological tumours

et al. 2016

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MicroRNA 15a, Inversely Correlated to PKCα, Is a Potential Marker to Differentiate between Benign and Malignant Renal Tumors in Biopsy and Urine Samples

Cited by 105 publications

References 37 publications

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

Protein Kinase C (PKC) Isozymes and Cancer

The translational potential of microRNAs as biofluid markers of urological tumours

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