Mir-200

위키백과, 우리 모두의 백과사전.

miR-200 마이크로RNA의 이차구조

분자 생물학에서 mir-200 mircoRNA는 짧은 RNA분자이다. 마이크로RNAmRNA에 붙고 그것이 잘라지게 하는 방법으로 번역을 막아 다른 유전자의 발현 정도를 조절한다. miR-200과는 miR-200a, miR-200b, miR-200c, miR-141, miR-429를 포함한다. miR-200 마이크로RNA가 전이에 연관이 있다는 증거는 속속히 드러나고 있다.[1]

게놈 위치[편집]

miR-200의 다섯 구성원은 두 가지의 클러스터에 존재한다. 사람에서는 miR-200a, miR-200b, miR-429는 염색체1번에 위치하고, miR-200c, miR-141은 염색체12번에 위치한다. 쥐에서는 두 클러스터가 염색체4번 6번에 위치한다.[1]

발현[편집]

miR-200과의 구성원은 상피조직에 풍부하다.[2]

암진행에 연관[편집]

miR-200과는 전이의 시작인 상피-간엽 전환(EMT, epithelial-mesenchymal transition)에 중요한 역할을 한다고 알려졌다. EMT는 배아 발생의 한 부분이며, 암의 진행과 많은 유사점을 공유한다. EMT과정에서 세포는 접착능력을 잃고 운동성이 증가한다. 이것은 E-캐드헤린발현의 억제로 나타나며 전이의 처음 과정이다.

대조적으로, miR-200은 전이의 마지막 단계를 촉진하는 것으로 보였으며 이것은 전이되는 암세포가 EMT의 반대과정인 MET를 전이되어 도착된 세포에서 콜로니를 형성할 때 일어난다. 쥐의 동형 암 세포 라인에서, miR-200과는 전이를 할 수 있는 세포(4T1세포)에서는 강하게 발현되지만, 콜로니를 형성 할 수 없는 세포(4TO7세포)에서는 발현되지 않았다. 비전이성세포인 4TO7세포에서 miR-200c의 과발현은 쉽게 MET를 가능하게 하였으며 간과 폐에 콜로니를 생성하였다.[3]

miR-200은 E-캐드헤린전사 억제자인 ZEB1ZEB2를 대상으로 한다. miR-141과 miR200b는 E-캐드헤린의 발현을 줄여서 세포의 이동능력을 증가시키고 EMT를 유발한다.[4][5]

[편집]

EMT와 진행에 있어서 miR-200의 역할은 연결되어있다:

각주[편집]

  1. Korpal M; Lee ES; Hu G; Kang Y (2008년 5월). “The miR-200 family inhibits epithelial-mesenchymal transition (EMT) and promotes mesenchymal-epithelial transition (MET) by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2”. 《J. Biol. Chem.》 283 (22): 14910–4. doi:10.1074/jbc.C800074200. PMID 18411277. 
  2. Lu J; Getz G; Miska EA; 외. (2005년 6월). “MicroRNA expression profiles classify human cancers”. 《Nature》 435 (7043): 834–8. doi:10.1038/nature03702. PMID 15944708. 
  3. Dykxhoorn DM (2010). “MicroRNAs and metastasis: little RNAs go a long way”. 《Cancer Res》 70 (16): 6401–6406. doi:10.1158/0008-5472.CAN-10-1346. PMC 2922433. PMID 20663901. 
  4. Gregory PA; Bert AG; Paterson EL; 외. (2008년 5월). “The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1”. 《Nat. Cell Biol.》 10 (5): 593–601. doi:10.1038/ncb1722. PMID 18376396. 
  5. Park SM; Gaur AB; Lengyel E; Peter ME (2008년 4월). “The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2”. 《Genes Dev.》 22 (7): 894–907. doi:10.1101/gad.1640608. PMC 2279201. PMID 18381893. 
  6. Adam L; Zhong M; Choi W; 외. (2009년 8월). “miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy”. 《Clin. Cancer Res.》 15 (16): 5060–72. doi:10.1158/1078-0432.CCR-08-2245. PMID 19671845. 
  7. Wiklund ED; Bramsen JB; Hulf T; 외. (2010년 5월). “Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer”. 《Int J Cancer》 128 (6): 1327–34. doi:10.1002/ijc.25461. PMID 20473948. 
  8. Tryndyak VP; Beland FA; Pogribny IP (2010년 7월). “E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells”. 《Int. J. Cancer》 126 (11): 2575–83. doi:10.1002/ijc.24972. PMID 19839049. 
  9. Dykxhoorn DM; Wu Y; Xie H; 외. (2009). Blagosklonny, Mikhail V., 편집. “miR-200 enhances mouse breast cancer cell colonization to form distant metastases”. 《PLoS ONE》 4 (9): e7181. doi:10.1371/journal.pone.0007181. PMC 2749331. PMID 19787069. 
  10. Elson-Schwab I; Lorentzen A; Marshall CJ (2010). Danen, Erik H. J., 편집. “MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion”. 《PLoS ONE》 5 (10): e13176. doi:10.1371/journal.pone.0013176. PMC 2949394. PMID 20957176. 
  11. Hu X; Macdonald DM; Huettner PC; Feng Z; El Naqa IM; Schwarz JK; Mutch DG; Grigsby PW; Powell SN; Wang X (2009). “A miR-200 microRNA cluster as prognostic marker in advanced ovarian cancer.”. 《Gynecol Oncol》 114 (3): 457–64. doi:10.1016/j.ygyno.2009.05.022. PMID 19501389. 
  12. Ali S; Ahmad A; Banerjee S; Padhye S; Dominiak K; Schaffert JM; Wang Z; Philip PA; Sarkar FH (2010). “Gemcitabine sensitivity can be induced in pancreatic cancer cells through modulation of miR-200 and miR-21 expression by curcumin or its analogue CDF.”. 《Cancer Res》 70 (9): 3606–17. doi:10.1158/0008-5472.CAN-09-4598. PMC 2978024. PMID 20388782. 
  13. Li Y; VandenBoom TG; Kong D; Wang Z; Ali S; Philip PA; Sarkar FH (2009). “Up-regulation of miR-200 and let-7 by natural agents leads to the reversal of epithelial-to-mesenchymal transition in gemcitabine-resistant pancreatic cancer cells.”. 《Cancer Res》 69 (16): 6704–12. doi:10.1158/0008-5472.CAN-09-1298. PMC 2727571. PMID 19654291. 
  14. Kong D; Li Y; Wang Z; Banerjee S; Ahmad A; Kim HR; Sarkar FH (2009). “miR-200 regulates PDGF-D-mediated epithelial-mesenchymal transition, adhesion, and invasion of prostate cancer cells.”. 《Stem Cells》 27 (8): 1712–21. doi:10.1002/stem.101. PMID 19544444. 
  15. Shinozaki A; Sakatani T; Ushiku T; Hino R; Isogai M; Ishikawa S; Uozaki H; Takada K; Fukayama M (2010). “Downregulation of microRNA-200 in EBV-associated gastric carcinoma.”. 《Cancer Res》 70 (11): 4719–27. doi:10.1158/0008-5472.CAN-09-4620. PMID 20484038. 
  16. Gibbons DL; Lin W; Creighton CJ; Rizvi ZH; Gregory PA; Goodall GJ; Thilaganathan N; Du L; Zhang Y; Pertsemlidis A; Kurie JM (2009). “Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression.”. 《Genes Dev》 23 (18): 2140–51. doi:10.1101/gad.1820209. PMC 2751985. PMID 19759262. 

참고 문헌[편집]

  1. Wiklund ED; Bramsen JB; Hulf T; Dyrskjøt L; Ramanathan R; Hansen TB; Villadsen SB; Gao S; Ostenfeld MS; Borre M; Peter ME; Ørntoft TF; Kjems J; Clark SJ. (2010). “Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer.”. 《Int J Cancer》 128 (6): 1327–34. doi:10.1002/ijc.25461. PMID 20473948. 
  2. Tryndyak VP; Beland FA; Pogribny IP (2010). “E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells.”. 《Int J Cancer》 126 (11): 2575–83. doi:10.1002/ijc.24972. PMID 19839049. 
  3. Elson-Schwab I; Lorentzen A; Marshall CJ (2010). Danen, Erik H. J., 편집. “MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion.”. 《PLoS ONE》 5 (10): e13176. doi:10.1371/journal.pone.0013176. PMC 2949394. PMID 20957176. 
  4. Dykxhoorn DM; Wu Y; Xie H; Yu F; Lal A; Petrocca F; Martinvalet D; Song E; Lim B; Lieberman J (2009). Blagosklonny, Mikhail V., 편집. “miR-200 enhances mouse breast cancer cell colonization to form distant metastases.”. 《PLoS ONE》 4 (9): e7181. doi:10.1371/journal.pone.0007181. PMC 2749331. PMID 19787069. 
  5. Iliopoulos D; Lindahl-Allen M; Polytarchou C; Hirsch HA; Tsichlis PN; Struhl K (2010). “Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.”. 《Mol Cell》 39 (5): 761–72. doi:10.1016/j.molcel.2010.08.013. PMC 2938080. PMID 20832727. 
  6. Adam L; Zhong M; Choi W; Qi W; Nicoloso M; Arora A; Calin G; Wang H; Siefker-Radtke A; McConkey D; Bar-Eli M; Dinney C (2009). “miR-200 expression regulates epithelial-to-mesenchymal transition in bladder cancer cells and reverses resistance to epidermal growth factor receptor therapy.”. 《Clin Cancer Res》 15 (16): 5060–72. doi:10.1158/1078-0432.CCR-08-2245. PMID 19671845. 
  7. Brabletz S; Brabletz T (2010). “The ZEB/miR-200 feedback loop--a motor of cellular plasticity in development and cancer?”. 《EMBO Rep》 11 (9): 670–7. doi:10.1038/embor.2010.117. PMC 2933868. PMID 20706219. 
  8. Mongroo PS; Rustgi AK (2010). “The role of the miR-200 family in epithelial-mesenchymal transition.”. 《Cancer Biol Ther》 10 (3): 219–22. doi:10.4161/cbt.10.3.12548. PMID 20592490. 
  9. Lin Z; Wang X; Fewell C; Cameron J; Yin Q; Flemington EK (2010). “Differential expression of the miR-200 family microRNAs in epithelial and B cells and regulation of Epstein-Barr virus reactivation by the miR-200 family member miR-429.”. 《J Virol》 84 (15): 7892–7. doi:10.1128/JVI.00379-10. PMC 2897641. PMID 20484493. 
  10. Teleman AA (2010). “miR-200 de-FOGs insulin signaling.”. 《Cell Metab》 11 (1): 8–9. doi:10.1016/j.cmet.2009.12.004. PMID 20085731. 
  11. Hyun S; Lee JH; Jin H; Nam J; Namkoong B; Lee G; Chung J; Kim VN (2009). “Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K.”. 《Cell》 139 (6): 1096–108. doi:10.1016/j.cell.2009.11.020. PMID 20005803. 
  12. Bendoraite A; Knouf EC; Garg KS; Parkin RK; Kroh EM; O'Briant KC; Ventura AP; Godwin AK; Karlan BY; Drescher CW; Urban N; Knudsen BS; Tewari M (2010). “Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition.”. 《Gynecol Oncol》 116 (1): 117–25. doi:10.1016/j.ygyno.2009.08.009. PMC 2867670. PMID 19854497. 
  13. Korpal M; Lee ES; Hu G; Kang Y (2008). “The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2.”. 《J Biol Chem》 283 (22): 14910–4. doi:10.1074/jbc.C800074200. PMID 18411277. 
  14. Gregory PA; Bert AG; Paterson EL; Barry SC; Tsykin A; Farshid G; Vadas MA; Khew-Goodall Y; Goodall GJ (2008). “The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.”. 《Nat Cell Biol》 10 (5): 593–601. doi:10.1038/ncb1722. PMID 18376396. 
  15. Park SM; Gaur AB; Lengyel E; Peter ME (2008). “The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.”. 《Genes Dev》 22 (7): 894–907. doi:10.1101/gad.1640608. PMC 2279201. PMID 18381893. 
  16. Spaderna S; Brabletz T; Opitz OG (2009). “The miR-200 family: central player for gain and loss of the epithelial phenotype.”. 《Gastroenterology》 136 (5): 1835–7. doi:10.1053/j.gastro.2009.03.009. PMID 19324106. 
  17. Peter ME (2009). “Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression.”. 《Cell Cycle》 8 (6): 843–52. doi:10.4161/cc.8.6.7907. PMC 2688687. PMID 19221491. 
  18. Korpal M; Kang Y (2008). “The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis.”. 《RNA Biol》 5 (3): 115–9. doi:10.4161/rna.5.3.6558. PMID 19182522. 
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  20. Bracken CP; Gregory PA; Kolesnikoff N; Bert AG; Wang J; Shannon MF; Goodall GJ (2008). “A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.”. 《Cancer Res》 68 (19): 7846–54. doi:10.1158/0008-5472.CAN-08-1942. PMID 18829540. 
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