Ebru ETEM ÖNALAN, Selcen GÖKTÜRK, Gökhan ARTAŞ, Asude AKSOY, Mustafa KOÇ, Ahmet TEKTEMUR, Asuman VAROĞLU

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siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line

siRNA-mediated stathmin1 silencing inhibits proliferation of prostate carcinoma cell line

Stathmin1 (STMN1) has been proposed as a possible prognostic marker and a potential therapeutic target for some cancers. We aimed to analyze the changes in autophagy, invasion, apoptosis-related genes in prostate cancer (PCa) cell line (PC-3), after small interfering RNA (siRNA)-mediated STMN1 silencing, and also the relationships of STMN1 expression, clinicopathological parameters, and survival (OS) in PCa cases. The STMN1 expressions were analyzed, immunohistochemically, in formalin-fixed paraffin-embedded 75 PCa and 15 benign prostatic hypertrophy (BPH) tissues. The correlation between the levels of expression STMN1, clinicopathological features, and OS was determined in PCa cases. The siRNA-mediated STMN1 incubated PC-3 cells were transfected and compared to negative control siRNAs. We determined mRNA levels in autophagy, invasion, and apoptosis genes with the combination of reverse transcriptionpolymerase chain reaction (RT-PCR) and western blotting in PC3 cell lines after STMN1 silencing. It was determined that STMN1 was overexpressed significantly in PCa cases, immunohistochemically. The overexpression of STMN1 was significantly correlated with the high-grade Gleason score, and it was associated with a worse prognosis of PCa cases according to the Kaplan–Meier survival analysis (p < 0.05). Significant silencing in STMN1 was determined (87.5%) after siRNA applications. Especially, invasion genes such as claudin 7, fibroblast growth factor 8, hypoxia-inducible factor 1 subunit alpha, hepatocyte growth factor, matrix metallopeptidase 2, 7 genes, markedly, decreased by siRNA-mediated STMN1silencing. STMN1 silencing was determined to significantly increase caspase 3 protein expression by using western blot analysis (p < 0.001). Although STMN1 silencing did not have a significant effect on the induction of apoptosis and autophagy-related genes in PCa cells, it was shown to affect apoptotic mechanisms through the caps3 protein. siRNA-mediated STMN1 silencing decreases proliferation in the PCa cell line. It is thought that STMN1 can serve as a potential therapeutic target in the advanced stage-PCa, especially.
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  • Aghababazadeh M, Dorraki N, Javan FA, Fattahi AS, Gharib M et al. (2017). Downregulation of Caspase 8 in a group of Iranian breast cancer patients - A pilot study. Journal of the Egyptian Nati-onal Cancer Institute 29 (4): 191-195. doi: 10.1016/j. jnci.2017.10.001.
  • Alli E, Bash-Babula J, Jin-Ming Y, Hait WN. (2021). Effect of stathmin on the sensitivity to anti-microtubule drugs in human breast cancer. Cancer Research 62 (23): 6864-6869.
  • Aldahl J, Mi J, Pineda A, Kim WK, Olson A, et al. (2020). Aberrant activation of hepatocyte growth factor/MET signaling promotes -catenin–mediated prostatic tumorigenesis. Journal of Bio-logical Chemistry 295 (2): 631-644. doi: 10.1074/jbc. RA119.011137
  • Akhtar J, Wang Z, Zhang ZP, Bi MM (2013). Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric cancer cells inhibits proliferation in vitro and tumor growth in vi-vo. Journal of Translational Medicine 11: 212. doi: 10.1186/1479-5876-11-212
  • Armstrong AJ (2018). Updates in advanced prostate cancer 2018. Prostate Cancer Prostatic Disea-ses 21 (4): 449-450. doi: 10.1038/s41391-018-0100-7
  • Bildik A, Bayar I (2018). Inhibition of apopitotic pathways in cancer. Turkiye Klinikleri Journal of Veterinary Sciences 9 (2): 42-51.
  • Chen Z, Wang T, Cai L, Su C, Zhong B et al. (2012). Clinicopathological significance of non-small cell lung cancer with high prevalence of Oct- 4 tumor cells. Journal of Experimental & Clinical Cancer Research 31 (1): 10. doi: 10.1186/1756-9966-31-10
  • Cristofani R, Marelli MM, Cicardi ME, Fontana F, Marzagalli M et al. (2018). Dual role of autop-hagy on docetaxel-sensitivity in prostate cancer cells. Cell Death & Disease 9 (9): 889. doi: 10.1038/s41419-018-0866-5
  • Dahiya N, Becker KG, Wood 3RD WH, Zhang Y, Morin PJ (2011). Claudin-7 is frequently ove-rexpressed in ovarian cancer and promotes invasion. PLoS One 6 (7): e22119. doi: 10.1371/ journal.pone.0022119
  • Friedrich B, Gronberg H, Landstrom M, Gullberg M, Bergh A (1995). Differentiation-stage speci-fic expression of oncoprotein 18 in human and rat prostatic adenocarcinoma. Prostate 27 (2): 102- 109. doi: 10.1002/pros.2990270207
  • Geng X, Chen C, Huang Y, Hou J (2020). The prognostic value and potential mechanism of Mat-rix Metalloproteinases among Prostate Cancer. International Journal of Medical Sciences 17 (11): 1550-1560. doi: 10.7150/ijms.46780
  • Ghosh R, Gu G, Tillman E, Yuan J, Wang Y et al. (2007). Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression. Prostate 67 (10): 1038- 1052. doi: 10.1002/pros.20601
  • Golouh R, Cufer T, Sadikov A, Nussdorfer P, Usher PA et al. (2008). The prognostic value of Stathmin-1, S100A2, and SYK proteins in ER-positive primary breast cancer patients treated with adjuvant tamoxifen monotherapy: an immunohistochemical study. Breast Cancer Research and Tre-atment 110 (2): 317– 326. doi: 10.1007/s10549-007-9724-3
  • Howell B, Larsson N, Gullberg M, Cassimeris L (1999) Dissociation of the tubulin-sequestering and microtubule catastrophepromoting activities of oncoprotein 18/stathmin. Molecular Biology of the Cell 10 (1): 105–118. doi: 10.1091/mbc.10.1.105.
  • Hu D, Jıang L, Luo S, Zhao X, Hu H et al. (2020). Development of on autophagy-related gene expression signature for prognosis prediction in prostate cancer patients. Journal of Translational Medicine 18 (1): 160. doi: 10.1186/s12967-020-02323-x
  • Huang KH, Fang WL, Li AFY, Liang PH, Wu CW et al. (2018). Caspase-3, a key apoptotic pro-tein, as a prognostic marker in gastric cancer after curative surgery. International Journal of Surgery 52: 258-263. doi: 10.1016/j.ijsu.2018.02.055
  • Luo Y, Li M, Zuo X, Basourakos SP, Zhang J et al. (2018). β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer. International Journal of Oncology 52 (6): 1827-1840. doi: 10.3892/ijo.2018.4368
  • Kimberly AB, Yan YY, Dominic CHN et al. (2015). Loss of miR223 and JNK Signaling Contri-bute to Elevated Stathmin in Malignant Pleural Mesothelioma. Molecular Cancer Research 13 (7): 1106-1118. doi: 10.1158/1541-7786.MCR-14-0442
  • Mattila MM, Härkönen PL (2007). Role of fibroblast growth factor 8 in growth and progression of hormonal cancer. Cytokine & Growth Factor Reviews 18 (3-4): 57–66. doi: 10.1016/j. cytogfr.2007.04.010
  • Malheiros CCC, Lourenco SV, Fonseca FP, Soares FA (2011). Claudin expression is dysregulated in prostate adenocarcinomas but does not correlate with main clinicopathological parameters. Pathology 43 (2): 143-148. doi: 10.1097/PAT.0b013e3283428099
  • Meng ZJ, Tao K (2016). Enhancement of Chemosensitivity by Stathmin-1 Silencing in Gastric Cancer Cells In Situ and In Vivo. Oncology Research 23 (1-2): 35-41. doi: 10.3727/09650 4015X14452563486057
  • Mistry SJ, Bank A, Atweh GF (2005). Targeting stathmin in prostate cancer. Molecular Cancer Therapeutics 4 (12): 1821-1829. doi: 10.1158/1535-7163.MCT-05-0215
  • Murillo-Garzón V, Kypta R (2017). WNT signalling in prostate cancer. Nature Reviews Urology 14 (11): 683-696 doi: 10.1038/ nrurol.2017.144
  • Murray NP, Reyes E, Salazar A, Lopez MA, Orrego S et al. (2020). The expression of matrix-metalloproteinase-2 in bone marrow micro-metastasis is associated with the presence of circulating prostate cells and a worse prognosis in men treated with radical prostatectomy for prostate cancer. Turkish Journal of Urology 146 (3): 186-195. doi: 10.5152/tud.2020.19219
  • NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Version 2. 2021. In: Pros-tate Cancer. (Last accessed on February 17, 2021). https://www.nccn.org/ professionals/physician_gls/pdf/prostate.pdf
  • Nie W, Xu MI-DIE, Gan L, Huang H, Xiu Q et al. (2015). Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer. Laboratory Investigation 95 (1): 56-64. doi: 10.1038/labinvest.2014.124
  • Onorati AV, Dyczynski M, Ojha R, Amaravadi RK. (2018). Targeting autophagy in cancer. Cancer 124: 3307-3318. doi: 10.1002/ cncr.31335 Pisters LL, Troncoso P, Zhau E, Li W, von Eschenbach AC et al. (1995). c-met proto-oncogene expression in benign and malignant human prostate tissues. Journal of Urology 154 (1): 293–298. Sha J, Han Q, Chi C, Zhu Y, Pan J et al. (2020). Upregulated KDM4B promotes prostate cancer cell proliferation by activating autophagy. Journal of Cellular Physiology 235 (3): 2129-2138. doi: 10.1002/jcp.29117 Siegel RL, Miller KD, Jemal A (2020). Cancer statistics, 2020. CA-A Cancer Journal for Clinici-ans 70 (1): 7-30. doi: 10.3322/ caac.21590 Singh AB, Dhawan P (2015). Claudins and cancer: Fall of the soldiers entrusted to protect the gate and keep the barrier intact. Seminars in Cell & Developmental Biology 42: 58-65. doi: 10.1016/j.semcdb.2015.05.001 Sucharita JM, George FA (2006). Therapeutic interactions between stathmin inhibition and che-motherapeutic agents in prostate cancer. Molecular Cancer Therapeutics 5 (12): 3248-357. doi: 10.1158/1535-7163.MCT-06-0227 Tanaka A, Miyamoto K, Matsuo H, Matsumoto K, Yoshida H (1995). Human androgen-induced growth factor in prostate and breast cancer cells: its molecular cloning and growth properties. FEBS Letters 363 (3): 226–230. doi: 10.1016/0014-5793(95)00324-3 Tran MGB, Bibby BAS, Yang L, Lo F, Warren AY, et al. (2020). Independence of HIF1a and androgen signaling pathways in prostate cancer. BMC Cancer 20(1): 469. doi: 10.1186/s12885- 020-06890-6.
  • Tregunna R. (2020) Serum MMP7 levels could guide metastatic therapy for prostate cancer. Nature Reviews Urology 17 (12): 658. doi: 10.1038/s41585-020-00396-3
  • Vlajnic T, Bubendorf L (2021). Molecular pathology of prostate cancer: a practical approach. Pat-hology 53 (1): 36-53. doi: 10.1016/j.pathol.2020.10.003
  • Wang J, Yao Y, Ming Y, Shen S, Wu N et al. (2016). Downregulation of stathmin 1 in human gallbladder carcinoma inhibits tumor growth in vitro and in vivo. Scientific Reports 6: 28833. doi: 10.1038/srep28833
  • Wu Y, Tang M, Wu Y, Weng X, Yang L et al. (2014). A combination of paclitaxel and siRNA-mediated silencing of Stathmin inhibits growth and promotes apoptosis of nasopharyngeal carcinoma cells. Cellular Oncology (Dordrecht) 37 (1): 53-67. doi: 10.1007/s13402-013-0163-3
  • Wroblewski LE, Piazuelo MB, Chaturvedi R, Schumacher M, Aihara E et al. (2015). Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut 64 (5): 720-730. doi: 10.1136/gutjnl-2014-307650
  • Williams K, Ghosh R, Giridhar PV, Gu G, Case T et al. (2012). Inhibition of stathmin1 accelerates the metastatic process. Cancer Research 72 (20): 5407-5417. doi: 10.1158/0008-5472. CAN-12-1158
  • Yan G, Ru Y, Wu K, Yan F, Wang Q et al. (2018). GOLM1 promotes prostate cancer progression through activating PI3K-Aktm TOR signaling. Prostate 78 (3): 166-177. doi: 10.1002/ pros.23461
Turkish Journal of Biology-Cover
  • ISSN: 1300-0152
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK
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