Original Articles

Reduced Expression Levels of the MST1 gene in the Peripheral Blood of Patients with Prostate Cancer

Abstract

 Background: Prostate cancer (PC) is the second most common malignancy in men, accounting for 12.5% of total number of cancers. The development of molecular studies (such as transcriptomics analysis) helps to characterization of Cancer, development of new targets for therapy, and introduction of the novel prognostic and diagnostic biomarkers. Recent studies have confirmed Mammalian Sterile 20-Like kinase (MST1) as a tumor suppressor gene. In this study we focus on MST1 expression level in WBC of PC patients, due to inheritance pattern of PC.  Material and Methods: This case-control study was conducted in two groups (20 patients with PC and 20 healthy individuals). After RNA extraction and cDNA synthesis, quantitative Real-Time PCR was done in order to determine the MST1 expression level. GAPDH was considered as internal control gene. Statistical analysis was performed by “Rotor-Gene Q series software 2.3.1” and “Rest 2.0.13 software”. Results: the study on 20 PC patients aged 50 to 70 years old and 20 healthy individuals shown that MST1 expression level in the WBC samples of PC patients have been reduced ≈62% compared to normal individuals. Conclusion: Introducing the reduced expression level of MST1 as a prostate cancer biomarker requires complementary research. However, in this study, biomarker validation and potential of MST1 has been approved
1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer. 2015;136(5):E359-E86.
2. Schulz W, Burchardt M, Cronauer M. Molecular biol- ogy of prostate cancer. Molecular human reproduction.
2003;9(8):437-48.
3. Brunet Vega A, Pericay C, Moya I, Ferrer A, Dotor E, Pisa A, et al. microRNA expression profile in stage III colorectal cancer: circulating miR-18a and miR-29a as promising bio- markers. Oncology reports. 2013;30(1):320-6.
4. Seidel C, Schagdarsurengin U, Blümke K, Würl P, Pfeif- er GP, Hauptmann S, et al. Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma. Molecular carcino- genesis. 2007;46(10):865-71.
5. Zhou D, Conrad C, Xia F, Park J-S, Payer B, Yin Y, et al.Mst1 and Mst2 maintain hepatocyte quiescence and suppress
hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer cell. 2009;16(5):425-38.
6. Rawat SJ, Chernoff J. Regulation of mammalian Ste20 (Mst) kinases. Trends in biochemical sciences. 015;40(3):149-56.
7. Gumbiner BM, Kim N-G. The Hippo-YAP signaling pathway and contact inhibition of growth. J Cell Sci.
2014; 127(4): 709-17.
8. O’Neill EE, Matallanas D, Kolch W. Mammalian sterile 20– like kinases in tumor suppression: An emerging pathway. Cancer research. 2005;65(13):5485-7.
9. Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, et al. Caspase-mediated activation and induc- tion of apoptosis by the mammalian Ste20-like kinase Mst1. EMBO J. 1998;17(8):2224-34.
10. Cinar B, Fang PK, Lutchman M, Di Vizio D, Adam RM, Pav- lova N, et al. The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. EMBO J.2007;26(21):4523-34.
11. Pan D. The hippo signaling pathway in development and cancer. Dev Cell. 2010;19(4):491-505.
12. Wong RS. Apoptosis in cancer: from pathogenesis to treat- ment. J Exp Clin Cancer Res. 2011;30:87.
13. Zhang W, Liu K, Pei Y, Ma J, Tan J, Zhao J. Mst1 regulates non-small cell lung cancer A549 cell apoptosis by inducing mitochondrial damage via ROCK1/Factin pathways. Int J Oncol. 2018.
14. Van de Laar E, Clifford M, Hasenoeder S, Kim BR, Wang D, Lee S, et al. Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/ MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas. Respir Res. 2014;15:160.
15. Yu J, Zhai X, Li X, Zhong C, Guo C, Yang F, et al. Iden- tification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach. Sci Rep.2017;7(1):14265.
16. Chunhua L, Zhao H, Zhao H, Lu Y, Wu J, Gao Z, et al. Clin-ical Significance of Peripheral Blood PCA3 Gene Expres-
sion in Early Diagnosis of Prostate Cancer. Transl Oncol.2018;11(3):628-32.
17. Pan D. The hippo signaling pathway in development and cancer. Developmental cell. 2010;19(4):491-505.
18. Wong RS. Apoptosis in cancer: from pathogenesis to treat-ment. Journal of Experimental & Clinical Cancer Research.
2011;30(1):87.
19. Kiraz Y, Adan A, Yandim MK, Baran Y. Major apoptotic mechanisms and genes involved in apoptosis. Tumor Biolo- gy. 2016;37(7):8471-86.
20. Lee Y-C, Yang C-N, Hsu T-I, Lu P-J. STK4 downregulation promotes tumor invasion/migration and is associated with poor prognosis in human colon cancer. AACR; 2013.
21. Minoo P, Zlobec I, Baker K, Tornillo L, Terracciano L, Jass JR, et al. Prognostic significance of mammalian ster- ile20-like kinase 1 in colorectal cancer. Modern pathology.2007;20(3):331.
22. Frau M, Biasi F, Feo F, Pascale RM. Prognostic markers and putative therapeutic targets for hepatocellular carcinoma. Molecular aspects of medicine. 2010;31(2):179-93.
23. Li W, Xiao J, Zhou X, Xu M, Hu C, Xu X, et al. STK4 reg- ulates TLR pathways and protects against chronic inflamma- tion–related hepatocellular carcinoma. The Journal of clini- cal investigation. 2015;125(11):4239-54.
24. Zhai X-H, Yu J-K, Yang F-Q, Zheng S. Identification of a new protein biomarker for colorectal cancer diagnosis. Mo- lecular medicine reports. 2012;6(2):444-8.
25. Mazaris E, Tsiotras A. Molecular pathways in prostate can- cer. Nephro-urology monthly. 2013;5(3):792.
26. Tang F, Zhang L, Xue G, Hynx D, Wang Y, Cron PD, et al. hMOB3 modulates MST1 apoptotic signaling and supports tumor growth in glioblastoma multiforme. Cancer research.2014.
27. Kim T-S, Lee D-H, Kim SK, Shin SY, Seo E-J, Lim D-S.Mammalian sterile 20-like kinase 1 (Mst1) suppresses lym-
phoma development by promoting faithful chromosome seg-regation. Cancer research. 2012:canres. 3956.2011.
28. Babel I, Barderas R, Díaz-Uriarte R, Martínez-Torrecuad- rada JL, Sánchez-Carbayo M, Casal JI. Identification of tu- mor-associated autoantigens for the diagnosis of colorectal cancer in serum using high density protein microarrays. Mo- lecular & cellular proteomics. 2009;8(10):2382-95.
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IssueVol 11 No 1 (2019) QRcode
SectionOriginal Articles
DOI https://doi.org/10.18502/bccr.v11i1.1648
Keywords
Prostate Cancer MST1 STK4 Hippo signaling Biomarker

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How to Cite
1.
Karimian F, Sahmani M, Maali A, Naserpour Farivar T, Karimi AA, Azad M. Reduced Expression Levels of the MST1 gene in the Peripheral Blood of Patients with Prostate Cancer. Basic Clin Cancer Res. 2019;11(1):27-34.