Expression profile of human tissue kallikrein 15 provides preliminary insights into its roles in the prostate and testis

Filippou, Panagiota; Ren, Annie; Soosaipillai, Antoninus; Papaioannou, Michail Dimitrios; Korbakis, Dimitrios; Safar, Roaa; Diamandis, Eleftherios P.; Conner, James

doi:10.1016/j.clinbiochem.2018.06.017

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…The hormonal regulation of KLK15 is controversial, some studies suggesting regulation by steroid hormones, while the others have not found such an effect. 10,50,51 Since we did not find any difference in AR expression between the aggressive cancer and control groups it is unlikely that the observed differences in expression of androgen-regulated KLKs are explained by AR expression.…”

Section: Discussionmentioning

confidence: 56%

“…Since the largest differences in mRNA levels between benign and cancerous prostatic tissues were observed in KLK12 and KLK15 levels, and their functions in PCa have not been well established, we investigated the effects of KLK12 and KLK15 down-regulation by RNAi. To this end, we used LNCaP cells, known to express both KLK12 and -15 47,50 and, as models for tumor growth, colony formation and proliferation. We observed that KLK15, but not KLK12, down-regulation consistently and significantly reduced colony formation of LNCaP cells grown on Matrigel basement membrane preparation.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

Lehto

Kovanen

Lintula

et al. 2023

Intl Journal of Cancer

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We aimed to study mRNA levels and prognostic impact of all 15 human kallikreinrelated peptidases (KLKs) and their targets, proteinase-activated receptors (PARs), in surgically treated prostate cancer (PCa). Seventy-nine patients with localized grade group 2-4 PCas represented aggressive cases, based on metastatic progression during median follow-up of 11 years. Eighty-six patients with similar baseline characteristics, but no metastasis during follow-up, were assigned as controls. Transcript counts were detected with nCounter technology. KLK12 protein expression was investigated with immunohistochemistry. The effects of KLK12 and KLK15 were studied in LNCaP cells using RNA interference. KLK3, -2, -4, -11, -15, -10 and -12 mRNA, in decreasing order, were expressed over limit of detection (LOD). The expression of KLK2, -3, -4 and -15 was decreased and KLK12 increased in aggressive cancers, compared to controls (P < .05). Low KLK2, -3 and -15 expression was associated with short metastasis-free survival (P < .05) in Kaplan-Meier analysis.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

Lehto

Kovanen

Lintula

et al. 2023

Intl Journal of Cancer

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“…[37,38] together with DNAJB6, ELAVL1, and NOS1AP, the latter through activation of tumor suppressor Scribble promoting neurogenesis [39][40][41][42]. ERN2, ELAVL1, KLK15, RRBP1, FOXD2, and HOXD8 FAM20C genes are directly involved in PC tumorigenesis, as well as, indirectly, SIKE1 and NOS1AP [43,44] and some of them have been suggested as prognostic biomarkers for PC [45][46][47][48][49][50][51][52][53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

Role of Epigenetic Therapy in the Modulation of Tumor Growth and Migration in Human Castration-Resistant Prostate Cancer Cells with Neuroendocrine Differentiation

et al. 2021

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Introduction: Neuroendocrine transdifferentiation (NED) of prostate cancer (PC) cells is associated with the development of resistance to antiandrogen therapy and poor prognosis in patients with castration-resistant PC (CRPC). Many of the molecular events, involved in NED, appear to be mediated by epigenetic mechanisms. In this study, we evaluated the antitumor activity and epigenetic modulation of 2 epigenetic drugs, such as the demethylating agent 5-aza-2′-deoxycytidine (AZA) and the methyl donor S-adenosylmethionine (SAM), in 2 human CRPC cell lines with NED (DU-145 and PC-3). Methods: The effects of AZA and SAM on cell viability, cell cycle, apoptosis, migration, and genome-wide DNA methylation profiling have been evaluated. Results: Both drugs showed a prominent antitumor activity in DU-145 and PC-3 cells, through perturbation of cell cycle progression, induction of apoptosis, and inhibition of cell migration. AZA and SAM reversed NED in DU-145 and PC-3, respectively. Moreover, AZA treatment modified DNA methylation pattern in DU-145 cells, sustaining a pervasive hypomethylation of the genome, with a relevant effect on several pathways involved in the regulation of cell proliferation, apoptosis, and cell migration, in particular Wnt/β-catenin. Conclusions: A relevant antitumor activity of these epigenetic drugs on CRPC cell lines with NED opens a new scenario in the therapy of this lethal variant of PC.

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“…Presently, we are unable to explain these findings and further studies are warranted. Along with its role in prostate cancer, the high expression of KLK15 confirms that the gene is implicated in spermatogenesis [ 61 ]. However, the mechanism by which the co-expression of upregulated DElncRNA with KLK15 affected sperm freezability remains unclear and would require further investigations.…”

Section: Discussionmentioning

confidence: 99%

Regulatory Potential of Long Non-Coding RNAs (lncRNAs) in Boar Spermatozoa with Good and Poor Freezability

Fraser

Paukszto

Mańkowska

et al. 2020

Life

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Long non-coding RNAs (lncRNAs) are suggested to play an important role in the sperm biological processes. We performed de novo transcriptome assembly to characterize lncRNAs in spermatozoa, and to investigate the role of the potential target genes of the differentially expressed lncRNAs (DElncRNAs) in sperm freezability. We detected approximately 4007 DElncRNAs, which were differentially expressed in spermatozoa from boars classified as having good and poor semen freezability (GSF and PSF, respectively). Most of the DElncRNAs were upregulated in boars of the PSF group and appeared to significantly affect the sperm’s response to the cryopreservation conditions. Furthermore, we predicted that the potential target genes were regulated by DElncRNAs in cis or trans. It was found that DElncRNAs of both freezability groups had potential cis- and trans-regulatory effects on different protein-coding genes, such as COX7A2L, TXNDC8 and SOX-7. Gene Ontology (GO) enrichment revealed that the DElncRNA target genes are associated with numerous biological processes, including signal transduction, response to stress, cell death (apoptosis), motility and embryo development. Significant differences in the de novo assembled transcriptome expression profiles of the DElncRNAs between the freezability groups were confirmed by quantitative real-time PCR analysis. This study reveals the potential effects of protein-coding genes of DElncRNAs on sperm functions, which could contribute to further research on their relevance in semen freezability.

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Expression profile of human tissue kallikrein 15 provides preliminary insights into its roles in the prostate and testis

Cited by 5 publications

References 42 publications

Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

Prognostic impact of kallikrein‐related peptidase transcript levels in prostate cancer

Role of Epigenetic Therapy in the Modulation of Tumor Growth and Migration in Human Castration-Resistant Prostate Cancer Cells with Neuroendocrine Differentiation

Regulatory Potential of Long Non-Coding RNAs (lncRNAs) in Boar Spermatozoa with Good and Poor Freezability

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