Circadian disruption by light-at-night aggravates tumorigenesis in Drosophila tumor model through upregulated unpaired2 (upd2)
Circadian disruption by light-at-night aggravates tumorigenesis in Drosophila tumor model through upregulated unpaired2 (upd2)
- 주제(키워드) unpaired2 (upd2) , circadian rhythm , tumorigenesis , yorkie (yki) , Drosophila melanogaster
- 발행기관 고려대학교 대학원
- 지도교수 이은일
- 발행년도 2019
- 학위수여년월 2019. 8
- 유형 Text
- 학위구분 석사
- 학과 대학원 의과학과
- 세부전공 의생명과학전공
- 원문페이지 71 p
- 실제URI http://www.dcollection.net/handler/korea/000000084959
- UCI I804:11009-000000084959
- DOI 10.23186/korea.000000084959.11009.0000936
- 본문언어 영어
- 제출원본 000046013550
초록/요약
Circadian disruption induced by light-at-night (LAN) could lead to breast and prostate cancer progression in shift-workers and in the general population living with artificial light. Several mechanisms, including reduction of melatonin secretion, have been suggested to explain how circadian disruption affects cancers. However, few studies have aimed to identify the molecular mechanisms of circadian disruption in cancers. We investigated the target molecules of circadian disruption in tumors using a yorkie (yki) overexpression Drosophila tumor model. Through exposure to 100 lux LAN for 10 days, circadian rhythm and sleep-wake behavior were severely disturbed in these flies. A rough eye surface in this tumor model is the representative phenotype of tumor morphology, and eye morphology was more roughly aggravated in the LAN exposure group along with loss of eye hairs than in the non-exposure group in the yki tumor model. Pathway finding using the KEGG mapper for RNA-sequencing analysis revealed several upregulated genes in the JAK/STAT pathway. We identified unpaired2 (upd2) as a possible candidate gene because it was upregulated and has been reported to be involved in aggravating tumorigenesis. Upd2 is a cytokine that activates the JAK/STAT pathway and is involved in cell growth and proliferation. To confirm the effect of upd2 on tumor aggravation associated with circadian disruption, we constructed a double mutant model with overexpression of yki and a null allele of upd2. Tumor aggravation by circadian disruption was alleviated in the double mutant, and the phenotype and gene expression were nearly identical to that of the control group, which was confirmed using an optical microscope, a scanning electron microscope, and qPCR. Stress resistance and geotaxis movement was recovered in the double mutant fly with the upd2 null allele. Therefore, upd2 might be a target gene related to circadian disruption and tumorigenesis.
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-Abstract
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-Introduction
-Material and Methods
-Results
-Discussion
-Abstract in Korean
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