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- 2017.1
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이 논문의 연구 히스토리 (2)
2017
Functional characterization of microRNA-200a-3p and long non-coding RNA GAS5 in the regulation of 5-fluorouracil resistance
이희진
의학세포생물학
2017.01
학위논문
microRNA-200a-3p increases 5-fluorouracil resistance by regulating dual specificity phosphatase 6 expression
이희진
,
김종태
,
강호인
외 6명
Experimental and Molecular Medicine
2017.01
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Acquisition of resistance to anti-cancer drugs is a significant obstacle to effective cancer treatment. Although several efforts have been made to overcome drug resistance in cancer cells, the detailed mechanisms have not been fully elucidated. Here, we investigated whether microRNAs (miRNAs) function as pivotal regulators in the acquisition of anti-cancer drug resistance to 5-fluorouracil (5-FU). A survey using a lentivirus library containing 572 precursor miRNAs revealed that five miRNAs promoted cell survival after 5-FU treatment in human hepatocellular carcinoma Hep3B cells. Among the five different clones, the clone expressing miR-200a-3p (Hep3B-miR-200a-3p) was further characterized as a 5-FU-resistant cell line. The cell viability and growth rate of Hep3B-miR-200a-3p cells were higher than those of control cells after 5-FU treatment. Ectopic expression of a miR-200a-3p mimic increased, while inhibition of miR-200a-3p downregulated, cell viability in response to 5-FU, doxorubicin, and CDDP (cisplatin). We also showed that dual-specificity phosphatase 6 (DUSP6) is a novel target of miR-200a-3p and regulates resistance to 5-FU. Ectopic expression of DUSP6 mitigated the pro-survival effects of miR-200a-3p. Taken together, these results lead us to propose that miR-200a-3p enhances anti-cancer drug resistance by decreasing DUSP6 expression.
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참고문헌 (29)
참고문헌 신청
Agarwal V / 2015 / Predicting effective microRNA target sites in mammalian mRNAs / Elife 4 : e05005 ~
Bartel DP. / 2004 / microRNAs: genomics, biogenesis, mechanism, and function / Cell 116 : 281 ~ 297
Bracken CP / 2014 / Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion / EMBO J 33 : 2040 ~ 2056
Bracken CP / 2015 / Network-based approaches to understand the roles of miR-200 and other microRNAs in cancer / Cancer Res 75 : 2594 ~ 2599
Calin GA / 2006 / microRNA signatures in human cancers / Nat Rev Cancer 6 : 857 ~ 866
Bartel DP. / 2004 / microRNAs: genomics, biogenesis, mechanism, and function / Cell 116 : 281 ~ 297
Bracken CP / 2014 / Genome-wide identification of miR-200 targets reveals a regulatory network controlling cell invasion / EMBO J 33 : 2040 ~ 2056
Bracken CP / 2015 / Network-based approaches to understand the roles of miR-200 and other microRNAs in cancer / Cancer Res 75 : 2594 ~ 2599
Calin GA / 2006 / microRNA signatures in human cancers / Nat Rev Cancer 6 : 857 ~ 866
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