The antitum our effect of miR ponPDAC celll in esisdiminished by dysbindin over expression

 D Zhu et al Cancer Letters Fig TheantitumoureffectofmiR ponPDACcelllinesisdiminishedbydysbindinoverexpression D. Zhu, et al. Cancer Letters 477 (2020) 107–121 Fig.7. TheantitumoureffectofmiR-342–3ponPDACcelllinesisdiminishedbydysbindinoverexpression,andmiR-342–3pdecreasesMDM2expression.(A)MiR- 342-3p-transfectedPDACcells(Aspc-1,Capan-2andPanc-1)werelessmetastaticandinvasivethancontrolcells.Thedataarepresentedasthemean ± SEM.(B) WesternblotanalysisshowingdysbindinproteinlevelsintheAspc-1-vector,Aspc-1-miR-342-mimicandAspc-1-miR-342-mimic+dysbindingroups.Thedataare presented as the mean ± SEM. (C) Transwell assays showing that dysbindin overexpression reverses the ability of miR-342–3p to inhibit PDAC cell (Aspc-1) migration and invasion. The data are presented as the mean ± SEM. (D) Western blot analysis showing MDM2 in miR-342-3p-transfected PDAC cells (Panc-1andBxpc-3)andcontrolcells.Thedataarepresentedasthemean ± SEM.(E)ProposedmodelbywhichtheNF-κB/MDM2signallingaxisisactivatedby dysbindin, which is regulated by miR-342–3p in PDAC cells. *P < 0.05, **P < 0.01, ***P < 0.001. Acknowledgements [12] C.H.Lee,Y.T.Jeon,S.H.Kim,Y.S.Song,NF-kappaBasapotentialmoleculartarget for cancer therapy, Biofactors (Oxford, England) 29 (2007) 19–35. [13] H.J. Kim, N. Hawke, A.S. Baldwin, NF-kappaB and IKK as therapeutic targets in This study was supported by grants from the National Key R&D cancer, Cell Death Differ. 13 (2006) 738–747. Program of China (No. 2017YFC1308600), Key Research and [14] S. Wang, Z. Liu, L. Wang, X. Zhang, NF-kappaB signaling pathway, inflammation and colorectal cancer, Cell. Mol. Immunol. 6 (2009) 327–334. Development Program of Shaanxi Province (No. 2017ZDXM-SF-024), [15] A. Oeckinghaus, S. Ghosh, The NF-kappaB family of transcription factors and its andNationalNaturalScienceFoundationofChina(No.81670563,No. regulation, Cold Spring Harbor perspectives in biology 1 (2009) a000034. 31900566). [16] V.Tergaonkar,M.Pando,O.Vafa,G.Wahl,I.Verma,p53stabilizationisdecreased upon NFkappaB activation: a role for NFkappaB in acquisition of resistance to The authors are grateful for technical support from Mingzuo Jiang chemotherapy, Canc. Cell 1 (2002) 493–503. (State Key Laboratory of Cancer Biology, National Clinical Research [17] M. Falasca, M. Kim, I. Casari, Pancreatic cancer: current research and future di- CenterforDigestiveDiseasesandXijingHospitalofDigestiveDiseases, rections, Biochim. Biophys. Acta 1865 (2016) 123–132. [18] F.B. Abreu, X. Liu, G.J. Tsongalis, miRNA analysis in pancreatic cancer: the Fourth Military Medical University) and Ning Xie (Department of Dartmouth experience, Clin. Chem. Lab. Med. 55 (2017) 755–762. Gastroenterology, the Second Affiliated Hospital of Xi\'an Jiaotong [19] Y (−)-Apomorphine. Gao, S.G. Zhang, Z.H. Wang, J.C. Liao, Down-regulation of miR-342-3p in he- University). patocellular carcinoma tissues and its prognostic significance, Eur. Rev. Med. Pharmacol. Sci. 21 (2017) 2098–2102. [20] K. Tao, J. Yang, Z. Guo, Y. Hu, H. Sheng, H. Gao, H. Yu, Prognostic value of miR- Appendix A. Supplementary data 221-3p, miR-342-3p and miR-491-5p expression in colon cancer, Am. J. Tourism Res. 6 (2014) 391–401. Supplementary data to this article can be found online at https:// [21] X. Guo, X. Lv, C. Fang, X. Lv, F. Wang, D. Wang, J. Zhao, Y. Ma, Y. Xue, Q. Bai, X. Yao, Y. Chen, Dysbindin as a novel biomarker for pancreatic ductal adeno- doi.org/10.1016/j.canlet.2020.02.033. carcinoma identified by proteomic profiling, Int. J. Canc. 139 (2016) 1821–1829. [22] C. Fang, X. Guo, X. Lv, R. Yin, X. Lv, F. Wang, J. Zhao, Q. Bai, X. Yao, Y. Chen, References Dysbindin promotes progression of pancreatic ductal adenocarcinoma via direct activation of PI3K, J. Mol. Cell Biol. 9 (2017) 504–515. [23] X.Chen,J.Qiu,D.Yang,J.Lu,C.Yan,X.Zha,Y.Yin,MDM2promotesinvasionand [1] A. Adamska, A. Domenichini, M. Falasca, Pancreatic ductal adenocarcinoma: cur- metastasis in invasive ductal b###http://www.glpbio.com/simage/GA11366-H-D-Leu-Thr-Arg-pNA-acetate-salt-3.png####reast carcinoma by inducing matrix metalloprotei- rent and evolving therapies, Int. J. Mol. Sci. 18 (2017) E1338. nase-9, PloS One 8 (2013) e78794. [2] H.Mangge,T.Niedrist,W.Renner,S.Lyer,C.Alexiou,J.Haybaeck,Newdiagnostic [24] Y.Chen,D.D.Wang,Y.P.Wu,D.Su,T.Y.Zhou,R.H.Gai,Y.Y.Fu,L.Zheng,Q.J.He, andtherapeuticaspectsofpancreaticductaladenocarcinoma,Curr.Med.Chem.24 H.Zhu,B.Yang,MDM2promotesepithelial-mesenchymaltransitionandmetastasis (2017) 3012–3024. of ovarian cancer SKOV3 cells, Br. J. Canc. 117 (2017) 1192–1201. [3] B.D. Krempley, K.H. Yu, Preclinical models of pancreatic ductal adenocarcinoma, [25] X. Lu, C. Yan, Y. Huang, D. Shi, Z. Fu, J. Qiu, Y. Yin, Mouse double minute 2 Chin. Clin. Oncol. 6 (2017) 25. (MDM2) upregulates Snail expression and induces epithelial-to-mesenchymal [4] A.D. Singhi, E.J. Koay, S.T. Chari, A. Maitra, Early detection of pancreatic cancer: transition in breast cancer in vitro and in vivo, Oncotarget 7 (2016) opportunities and challenges, Gastroenterology 156 (2019) 2024–2040. 37177–37191. [5] D.P. Ryan, T.S. Hong, N. Bardeesy, Pancreatic adenocarcinoma, N. Engl. J. Med. [26] A. Roszak, M. Misztal, A. Sowinska, P.P. Jagodzinski, Murine double-minute 2 371 (2014) 1039–1049. homologsinglenucleotidepolymorphisms285and309incervicalcarcinogenesis, [6] E.I. Petit, Z. Michalak, R. Cox, C.M. O\'Tuathaigh, N. Clarke, O. Tighe, K. Talbot, Mol. Diagn. Ther. 19 (2015) 235–244. D. Blake, J. Joel, A. Shaw, S.A. Sheardown, A.D. Morrison, S. Wilson, [27] L. Liu, L. Yang, H. Chang, Y.N. Chen, F. Zhang, S. Feng, J. Peng, C.C. Ren, E.M.Shapland,D.C.Henshall,J.N.Kew,B.P.Kirby,J.L.Waddington,Dysregulation X BYL-719.A. Zhang, CP31398 attenuates endometrial cancer cell invasion, metastasis and of specialized delay/interference-dependent working memory following loss of resistance to apoptosis by downregulating MDM2 expression, Int. J. Oncol. 54 dysbindin-1A in schizophrenia-related phenotypes, Neuropsychopharmacology : (2019) 942–954. official publication of the American College of Neuropsychopharmacology 42 [28] C. Fu, D. Chen, R. Chen, Q. Hu, G. Wang, The schizophrenia-related protein dys- (2017) 1349–1360. bindin-1Aisdegradedandfacilitates NF-kappaBactivityinthenucleus,PloSOne [7] J. Larimore, S.A. Zlatic, M. Arnold, K.S. Singleton, R. Cross, H. Rudolph, 10 (2015) e0132639. M.V. Bruegge, A. Sweetman, C. Garza, E. Whisnant, V. Faundez, Dysbindin defi- [29] C. Vorvis, M. Koutsioumpa, D. Iliopoulos, Developments in miRNA gene signaling ciency modifies the expression of GABA neuron and ion permeation transcripts in pathways in pancreatic cancer, Future oncology (London, England) 12 (2016) the developing Hippocampus, Front. Genet. 8 (2017) 28. 1135–1150. [8] S. Wang, Y. Zhao, A. Aguilar, D. Bernard, C.Y. Yang, Targeting the MDM2-p53 [30] X. Xue, X. Fei, W. Hou, Y. Zhang, L. Liu, R. Hu, miR-342-3p suppresses cell pro- protein-protein interaction for new cancer therapy: progress and challenges, Cold liferation and migration by targeting AGR2 in non-small cell lung cancer, Canc. Spring Harbor perspectives in medicine 7 (2017) a026245 Belinostat (PXD101). Lett. 412 (2018) 170–178. [9] J.D. Oliner, A.Y. Saiki, S. Caenepeel, The role of MDM2 amplification and over- [31] Z. Cui, Y. Zhao, microRNA-342-3p targets FOXQ1 to suppress the aggressive phe- expressionintumorigenesis,ColdSpringHarborperspectivesinmedicine6(2016) notype of nasopharyngeal carcinoma cells, BMC Canc. 19 (2019) 104. a026336. [32] X.R. Li, H.J. Chu, T. Lv, L. Wang, S.F. Kong, S.Z. Dai, miR-342-3p suppresses pro- [10] C.M. Eischen, Role of Mdm2 and mdmx in DNA repair, J. Mol. Cell Biol. 9 (2017) liferation, migration and invasion by targeting FOXM1 in human cervical cancer, 69–73. FEBS Lett. 588 (2014) 3298–3307. [11] O.Karni-Schmidt,M.Lokshin,C.Prives,TherolesofMDM2andMDMXincancer, Annual review of pathology 11 (2016) 617–644. 121

Comments

Post a Comment

Popular posts from this blog

The cells were counterstained with DAPI for Apoptosis rates were determined by Annexin V-/PI double staining 10 min

 C. Zhao, et al. Cancer Letters 481 (2020) 15–23 were calculated. for5min.Afterblockingwith5%bovineserumalbumin(BSA)/PBSfor 1 h, the cells were sequentially incubated with the primary antibodies 2.4. Annexin V/PI staining and Alexa Fluor-conjugated secondary (Abcam) at room temperature for 1 h. The cells were counterstained with DAPI for Apoptosis rates were determined by Annexin V-/PI double staining 10 min, and observed with a confocal laser microscope (Zeiss LSM510 as previously described[22]. Thesuitably treated cells wereharvested, Meta, Germany). washedwithabindingbuffer(Sigma-Aldrich),andthenincubatedwith 0.3μlAnnexinV-FITCandPIin100μlbindingbufferfor15mininthe 2.10. Xenograft model dark. The stained cells were observed under an inverted fluorescence microscope equipped with a digital camera (Axio Observer Z1, Zeiss, Nude BALB/c mice (male, 5-weeks old, weighing 18–22 g) were Germany). obtained from Guangdong Laboratory Animal Monitoring Institute (SCXK2008-2002), and
Read more

Control cells were incubated without mon- MYB inhibition is feasible and has therapeutic potential

M.V. Yusenko, et al. Cancer Letters 479 (2020) 61–70 I B) genes, leading to disruption of the 3′-end of MYB mRNA, loss of Isolation of polyadenylated RNA and Northern blotting was performed MYB negative regulatory elements, and overexpression of oncogenic as described before [34]. Blots were hybridized sequentially to radi- MYB-NFIB fusion proteins [13]. MYB may also be activated by copy olabeled probes specific for MYB and ribosomal protein S17 mRNAs. numbergainorjuxtapositionofenhancerelementsfromNFIBandother Radioactive bands were quantified with a phosphor image analyzer. fusion partner genes [16,17]. Overall, thesefindings have greatly stimulated the interest in MYB 2.4. Flow cytometry as a target for drug development [1,3,18]. Although transcription fac- torsaretraditionally considereddifficulttotarget,initialapproaches to Approximately one million were cultured for 2 days in RPMI inhibit MYB activity or expression by small molecule or peptido-mi- 1640 medium containing 10
Read more

Dysbindin promotes PDAC metastasis and invasion in vitro and in vivo

 D. Zhu, et al. Cancer Letters 477 (2020) 107–121 Fig. 1. Dysbindin promotes PDAC metastasis and invasion in vitro and in vivo. (A) Western blot analysis showing dysbindin expression in PDAC and human pancreatic ductal epithelial cells. The data are presented as the mean ± SEM. (B) Western blotting and qRT-PCR analysis showing dysbindin expression in dysbindin-overexpressingcells(Aspc-1-LV-dysbindinandBxpc-3-LV-dysbindin)andcontrolcells(Aspc-1-LV-vectorandBxpc-3-LV-vector).Thedataarepresentedas themean ± SEM.(C)AfterPanc-1andCapan-2cellsweretransfectedwithLV-shDysbindin(sh1andsh2)orLV-shVector cck8 price ,WesternblottingandqRT-PCRanalysis wereperformed tomeasuredysbindinexpression.Thedataarepresentedasthe mean ± SEM.(D)OverexpressionofdysbindinenhancedAspc-1andBxpc-3cell migrationandinvasion.Thedataarepresentedasthemean ± SEM.(E)DysbindinknockdowndecreasedPanc-1andCapan-2cellmigrationandinvasion.Thedata are presented as the mean ± SEM. (F) In vivo metastasis assays.  Four
Read more