Home Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
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Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology

  • Panagiotis G. Adamopoulos , Christos K. Kontos ORCID logo and Andreas Scorilas ORCID logo EMAIL logo
Published/Copyright: June 6, 2018

Abstract

Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional characteristics. In this study, we describe the molecular cloning of four novel splice variants of the human KLK11 and KLK12 genes, discovered by combining 3′ rapid amplification of cDNA ends (3′ RACE), next-generation sequencing (NGS) technology, advanced bioinformatic analysis and Sanger sequencing. Expression analysis of these new transcripts in cell lines originating from 17 cancerous and two normal tissues revealed the expression pattern of each transcript. These novel KLK11 and KLK12 splice variants represent new potential cancer biomarkers.

References

Adamopoulos, P.G., Kontos, C.K., and Scorilas, A. (2017a). Identification and molecular cloning of novel transcripts of the human kallikrein-related peptidase 10 (KLK10) gene using next-generation sequencing. Biochem. Biophys. Res. Commun. 487, 776–781.10.1016/j.bbrc.2017.04.078Search in Google Scholar PubMed

Adamopoulos, P.G., Kontos, C.K., and Scorilas, A. (2017b). Molecular cloning of novel transcripts of human kallikrein-related peptidases 5, 6, 7, 8 and 9 (KLK5 – KLK9), using next-generation sequencing. Sci. Rep. 7, 17299.10.1038/s41598-017-16269-6Search in Google Scholar PubMed PubMed Central

Alexopoulou, D.K., Kontos, C.K., Christodoulou, S., Papadopoulos, I.N., and Scorilas, A. (2014). KLK11 mRNA expression predicts poor disease-free and overall survival in colorectal adenocarcinoma patients. Biomark. Med. 8, 671–685.10.2217/bmm.13.151Search in Google Scholar PubMed

Avgeris, M. and Scorilas, A. (2016). Kallikrein-related peptidases (KLKs) as emerging therapeutic targets: focus on prostate cancer and skin pathologies. Expert Opin. Ther. Targets 20, 801–818.10.1517/14728222.2016.1147560Search in Google Scholar PubMed

Avgeris, M., Mavridis, K., and Scorilas, A. (2010). Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies. Biol. Chem. 391, 505–511.10.1515/bc.2010.056Search in Google Scholar PubMed

Borgono, C.A. and Diamandis, E.P. (2004). The emerging roles of human tissue kallikreins in cancer. Nat. Rev. Cancer 4, 876–890.10.1038/nrc1474Search in Google Scholar PubMed

Clark, H.F., Gurney, A.L., Abaya, E., Baker, K., Baldwin, D., Brush, J., Chen, J., Chow, B., Chui, C., Crowley, C., et al. (2003). The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 13, 2265–2270.10.1101/gr.1293003Search in Google Scholar PubMed PubMed Central

Geng, X., Liu, Y., Diersch, S., Kotzsch, M., Grill, S., Weichert, W., Kiechle, M., Magdolen, V., and Dorn, J. (2017). Clinical relevance of kallikrein-related peptidase 9, 10, 11, and 15 mRNA expression in advanced high-grade serous ovarian cancer. PLoS One 12, e0186847.10.1371/journal.pone.0186847Search in Google Scholar PubMed PubMed Central

Kurlender, L., Borgono, C., Michael, I.P., Obiezu, C., Elliott, M.B., Yousef, G.M., and Diamandis, E.P. (2005). A survey of alternative transcripts of human tissue kallikrein genes. Biochim. Biophys. Acta 1755, 1–14.10.1016/j.bbcan.2005.02.001Search in Google Scholar PubMed

Planque, C., Choi, Y.H., Guyetant, S., Heuze-Vourc’h, N., Briollais, L., and Courty, Y. (2010). Alternative splicing variant of kallikrein-related peptidase 8 as an independent predictor of unfavorable prognosis in lung cancer. Clin. Chem. 56, 987–997.10.1373/clinchem.2009.138917Search in Google Scholar PubMed

Sano, A., Sangai, T., Maeda, H., Nakamura, M., Hasebe, T., and Ochiai, A. (2007). Kallikrein 11 expressed in human breast cancer cells releases insulin-like growth factor through degradation of IGFBP-3. Int. J. Oncol. 30, 1493–1498.10.3892/ijo.30.6.1493Search in Google Scholar

Shaw, J.L. and Diamandis, E.P. (2007). Distribution of 15 human kallikreins in tissues and biological fluids. Clin. Chem. 53, 1423–1432.10.1373/clinchem.2007.088104Search in Google Scholar PubMed

Talieri, M., Devetzi, M., Scorilas, A., Pappa, E., Tsapralis, N., Missitzis, I., and Ardavanis, A. (2012). Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact. Tumour Biol. 33, 1075–1084.10.1007/s13277-012-0347-xSearch in Google Scholar PubMed

Venables, J.P. (2006). Unbalanced alternative splicing and its significance in cancer. Bioessays 28, 378–386.10.1002/bies.20390Search in Google Scholar PubMed

Wen, Y.G., Wang, Q., Zhou, C.Z., Yan, D.W., Qiu, G.Q., Yang, C., Tang, H.M., and Peng, Z.H. (2011). Identification and validation of kallikrein-ralated peptidase 11 as a novel prognostic marker of gastric cancer based on immunohistochemistry. J. Surg. Oncol. 104, 516–524.10.1002/jso.21981Search in Google Scholar PubMed

Yoon, H., Laxmikanthan, G., Lee, J., Blaber, S.I., Rodriguez, A., Kogot, J.M., Scarisbrick, I.A., and Blaber, M. (2007). Activation profiles and regulatory cascades of the human kallikrein-related peptidases. J. Biol. Chem. 282, 31852–31864.10.1074/jbc.M705190200Search in Google Scholar PubMed

Yoshida, S., Taniguchi, M., Suemoto, T., Oka, T., He, X., and Shiosaka, S. (1998). cDNA cloning and expression of a novel serine protease, TLSP. Biochim. Biophys. Acta 1399, 225–228.10.1016/S0167-4781(98)00116-XSearch in Google Scholar

Yousef, G.M., Chang, A., Scorilas, A., and Diamandis, E.P. (2000a). Genomic organization of the human kallikrein gene family on chromosome 19q13.3-q13.4. Biochem. Biophys. Res. Commun. 276, 125–133.10.1006/bbrc.2000.3448Search in Google Scholar PubMed

Yousef, G.M., Magklara, A., and Diamandis, E.P. (2000b). KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer. Genomics 69, 331–341.10.1006/geno.2000.6346Search in Google Scholar PubMed

Zhang, J., Sun, X., Qian, Y., and Maquat, L.E. (1998). Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm. RNA 4, 801–815.10.1017/S1355838298971849Search in Google Scholar PubMed PubMed Central


Supplementary Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2017-0294).


Received: 2017-11-27
Accepted: 2018-04-15
Published Online: 2018-06-06
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Highlight: The 7th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  3. Obituary
  4. Manfred Schmitt (1947–2018)
  5. Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil
  6. Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer
  7. Kallikrein-related peptidases in lung diseases
  8. The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer
  9. Mining human cancer datasets for kallikrein expression in cancer: the ‘KLK-CANMAP’ Shiny web tool
  10. Specificity profiling of human trypsin-isoenzymes
  11. Activation and activity of glycosylated KLKs 3, 4 and 11
  12. Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
  13. Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
  14. Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases
  15. Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
  16. Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
  17. Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin
  18. Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
  19. Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
  20. Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype
  21. KLK5, a novel potential suppressor of vaginal carcinogenesis
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