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Ip8'ӿq> 3g? 3g?7ɻw'Nޝr司W'>N:up[6t.C `#?9sMs}[l[lctlAtlIǖtlI0 `tAtAtAtAtAtAtAtA0/`| _0/`u#'f0YGh0̀pp ,``SB0)}0)L!` SB0L'`: NpÔOp0hJ~a/+:O&Ij4Uד~7=qM'Ę4oQ1}ۥ,زZ:h 5@kZh 5@k\ƿ h#`0` &  0`0`> endobj 270 0 obj <> endobj 271 0 obj <>stream application/pdf RNA Interference-Mediated Knockdown onDKC1 Gene in Chemosensitized CRC CellLines Background Dyskerin (DKC1) gene, a tolemerase ribonucleoprotein complex, has been reported to be up-regulated in various sporadic cancers, including colorectal cancer (CRC). This study was performed to investigate its potential as a therapeutic target for CRC. Materials and Methods The RNA interference (RNAi) technique was employed to down-regulate DKC1 expression in two human CRC cell lines, HCT116 and HT-29, and followed by5-fluorouracil (5-FU) treatment. Functional assays were carried out. The efficacy of RNAi was assessed by quantitative polymerase chain reaction (qPCR) and Western blotting. Results RNAi targeting DKC1 reduced mRNA and protein levels significantly after 48 and 72 hours post-transfection respectively with concomitant decrease in cell viability (P<0.05) in both cell lines. HCT116 cells were arrested in G1 phase of the cell cycle. 5-FU treatment following silencing further reduced cell viability and arrested HCT116 cells in G2 phase. RNAi treatment also reduced HCT116 cell migration significantly. Conclusion Silencing of DKC1 in combination with 5-FU may represent a good strategy to inhibit the CRC growth. © 2015 Ting T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tammy Ting Rahman Jamal Roslan Harun Wan Zurinah Wan Ngah andNorfilza Mohd Mokhtar Colorectal cancer RNA Interference 5-Fluorouracil DKC1 protein Cell cycle 2016-07-25T16:53:56+05:30 2016-07-25T16:53:57+05:30 2016-07-25T16:53:57+05:30 Adobe InDesign CS6 (Windows) uuid:8e2a6514-0546-4eb4-8b44-5df931f5823d xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:A87B8E3E5A52E611B951B1C8516E4B81 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-07-25T16:53:56+05:30 xmp.iid:A77B8E3E5A52E611B951B1C8516E4B81 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Citation: Jargin SV, Kaloshin AK (2015) Back tothe Mechanisms of Cancer Incidence Increase afterChernobyl. Int J Cancer Res Mol Mech 1(2): doihttp://dx.doi.org/10.16966/ijcrmm.105 Norfilza Mohd Mokhtar, UKM Medical Molecular Biology Institute,Universiti Kebangsaan Malaysia, Jalan Ya’acob Latiff, 56000 Cheras, KL, Malaysia, Tel: 00603 91718459; Fax:006 003 91717185; E-mail: norfilza@ppukm.ukm.edu.my Adobe PDF Library 10.0.1 False endstream endobj 272 0 obj <> endobj xref 0 1193 0000000000 65535 f 0000287137 00000 n 0000287605 00000 n 0000287629 00000 n 0000297326 00000 n 0000297394 00000 n 0000297477 00000 n 0000308925 00000 n 0000309202 00000 n 0000309369 00000 n 0000309392 00000 n 0000309693 00000 n 0000309753 00000 n 0000310376 00000 n 0000310401 00000 n 0000310536 00000 n 0000318182 00000 n 0000321088 00000 n 0000321125 00000 n 0000324033 00000 n 0000324070 00000 n 0000327092 00000 n 0000327129 00000 n 0000330035 00000 n 0000330072 00000 n 0000347516 00000 n 0000382443 00000 n 0000445814 00000 n 0000463333 00000 n 0000463418 00000 n 0000463478 00000 n 0000464057 00000 n 0000464192 00000 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0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f 0000000000 65535 f trailer <]>> startxref 116 %%EOF 271 0 obj <>stream application/pdf RNA Interference-Mediated Knockdown onDKC1 Gene in Chemosensitized CRC CellLines Background Dyskerin (DKC1) gene, a tolemerase ribonucleoprotein complex, has been reported to be up-regulated in various sporadic cancers, including colorectal cancer (CRC). This study was performed to investigate its potential as a therapeutic target for CRC. Materials and Methods The RNA interference (RNAi) technique was employed to down-regulate DKC1 expression in two human CRC cell lines, HCT116 and HT-29, and followed by5-fluorouracil (5-FU) treatment. Functional assays were carried out. The efficacy of RNAi was assessed by quantitative polymerase chain reaction (qPCR) and Western blotting. Results RNAi targeting DKC1 reduced mRNA and protein levels significantly after 48 and 72 hours post-transfection respectively with concomitant decrease in cell viability (P<0.05) in both cell lines. HCT116 cells were arrested in G1 phase of the cell cycle. 5-FU treatment following silencing further reduced cell viability and arrested HCT116 cells in G2 phase. RNAi treatment also reduced HCT116 cell migration significantly. Conclusion Silencing of DKC1 in combination with 5-FU may represent a good strategy to inhibit the CRC growth. © 2015 Ting T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Tammy Ting Rahman Jamal Roslan Harun Wan Zurinah Wan Ngah andNorfilza Mohd Mokhtar Colorectal cancer RNA Interference 5-Fluorouracil DKC1 protein Cell cycle 2016-07-25T16:53:56+05:30 2016-07-25T16:54+05:30 2016-07-25T16:54+05:30 Adobe InDesign CS6 (Windows) uuid:1ce2dd30-ab65-47f7-a71f-607038003f50 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:A87B8E3E5A52E611B951B1C8516E4B81 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-07-25T16:53:56+05:30 xmp.iid:A77B8E3E5A52E611B951B1C8516E4B81 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Citation: Jargin SV, Kaloshin AK (2015) Back tothe Mechanisms of Cancer Incidence Increase afterChernobyl. Int J Cancer Res Mol Mech 1(2): doihttp://dx.doi.org/10.16966/ijcrmm.105 Norfilza Mohd Mokhtar, UKM Medical Molecular Biology Institute,Universiti Kebangsaan Malaysia, Jalan Ya’acob Latiff, 56000 Cheras, KL, Malaysia, Tel: 00603 91718459; Fax:006 003 91717185; E-mail: norfilza@ppukm.ukm.edu.my Adobe PDF Library 10.0.1 False endstream endobj 272 0 obj <> endobj 1194 0 obj <>/Metadata 271 0 R/Names 1195 0 R/Outlines 216 0 R/PageMode/UseOutlines/Pages 270 0 R/StructTreeRoot 273 0 R/Type/Catalog/ViewerPreferences<>>> endobj xref 0 1 0000000000 65535 f 271 2 0000638419 00000 n 0000646193 00000 n 1194 1 0000647665 00000 n trailer <<736BC52039EA934492326860CAECBA51>]/Prev 116>> startxref 647869 %%EOF