Browsing by Author "Tezcan, Gulcin"
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Publication Early-stage colon cancer with high malat1 expression is associated with the 5-fluorouracil resistance and future metastasis(Springer, 2022-07-06) Öztürk, Ersin; Aksoy, Seçil Ak; Tunca, Berrin; TUNCA, BERRİN; Erçelik, Melis; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; UĞRAŞ, NESRİN; YILMAZLAR, AHMET TUNCAY; Yerci, Omer; YERCİ, ÖMER; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-5956-8755; 0000-0001-8593-5101; 0000-0002-3820-424X; ADM-8457-2022; AAH-3843-2020Background This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). Methods and Results The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. Results High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. Conclusion MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.Publication Therapeutic potential of pharmacological targeting nlrp3 inflammasome complex in cancer(Frontiers Media Sa, 2021-02-03) Garanina, Ekaterina E.; Alsaadi, Mohammad; Gilazieva, Zarema E.; Martinova, Ekaterina, V; Markelova, Maria, I; Arkhipova, Svetlana S.; Hamza, Shaimaa; McIntyre, Alan; Rizvanov, Albert A.; Khaiboullina, Svetlana F.; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi.; 0000-0002-5956-8755; 0000-0001-7445-2091; 0000-0002-4082-515X; 0000-0002-5012-4760; 0000-0002-4791-7292; 0000-0002-9427-5739; AAH-3843-2020; H-4486-2013; HTO-8900-2023; AAE-4652-2022; AAP-5140-2021; W-9788-2018; P-4183-2017IntroductionDysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1 beta. However, the effect of NLRP3 complex formation on tumor progression remains controversial. Therefore, we sought to determine the effect of NLRP3 modulation on the growth of the different types of cancer cells, derived from lung, breast, and prostate cancers as well as neuroblastoma and glioblastoma in-vitro.MethodThe effect of Caspase 1 inhibitor (VX765) and combination of LPS/Nigericin on NLRP3 inflammasome activity was analyzed in A549 (lung cancer), MCF-7 (breast cancer), PC3 (prostate cancer), SH-SY5Y (neuroblastoma), and U138MG (glioblastoma) cells. Human fibroblasts were used as control cells. The effect of VX765 and LPS/Nigericin on NLRP3 expression was analyzed using western blot, while IL-1 beta and IL-18 secretion was detected by ELISA. Tumor cell viability and progression were determined using Annexin V, cell proliferation assay, LDH assay, sphere formation assay, transmission electron microscopy, and a multiplex cytokine assay. Also, angiogenesis was investigated by a tube formation assay. VEGF and MMPs secretion were detected by ELISA and a multiplex assay, respectively. Statistical analysis was done using one-way ANOVA with Tukey's analyses and Kruskal-Wallis one-way analysis of variance.ResultsLPS/Nigericin increased NRLP3 protein expression as well as IL-1 beta and IL-18 secretion in PC3 and U138MG cells compared to A549, MCF7, SH-SY5Y cells, and fibroblasts. In contrast, MIF expression was commonly found upregulated in A549, PC3, SH-SY5Y, and U138MG cells and fibroblasts after Nigericin treatment. Nigericin and a combination of LPS/Nigericin decreased the cell viability and proliferation. Also, LPS/Nigericin significantly increased tumorsphere size in PC3 and U138MG cells. In contrast, the sphere size was reduced in MCF7 and SH-SY5Y cells treated with LPS/Nigericin, while no effect was detected in A549 cells. VX765 increased secretion of CCL24 in A549, MCF7, PC3, and fibroblasts as well as CCL11 and CCL26 in SH-SY5Y cells. Also, VX765 significantly increased the production of VEGF and MMPs and stimulated angiogenesis in all tumor cell lines.DiscussionOur data suggest that NLRP3 activation using Nigericin could be a novel therapeutic approach to control the growth of tumors producing a low level of IL-1 beta and IL-18.