Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR
- Authors
- Chae, HJ[Chae, Hae-Jung]; Seo, JB[Seo, Jong Bae]; Kim, SH[Kim, Sung-Hak]; Jeon, YJ[Jeon, Young-Jun]; Suh, SS[Suh, Sung-Suk]
- Issue Date
- 2021
- Publisher
- IVYSPRING INT PUBL
- Keywords
- Fhit; miRNAs; tumor suppressor; Let-7; Lin28b
- Citation
- INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, v.18, no.3, pp.706 - 714
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
- Volume
- 18
- Number
- 3
- Start Page
- 706
- End Page
- 714
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/93471
- DOI
- 10.7150/ijms.51429
- ISSN
- 1449-1907
- Abstract
- Objective: Fhit gene is known as a genome "caretaker" and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role of Fhit in regulating Lin28 and microRNAs (miRNAs) loop. Material and Methods: To this end, we employed Fhit overexpressing isogenic cell lines to conduct miRNA nanostring array, and differentially expressed miRNAs were identified. Using real-time PCR and Western blot analysis, expression levels of Lin28b or miRNAs were investigated in response to the overexpression of Fhit gene in H1299 lung cancer cells. Results: A series of in vitro including gene nanostring analyses revealed that Lin28B protein was induced by Fhit gene overexpression, which consequently suppressed Let-7 miRNAs. Also, we found that miRNAs in miR-17/92 clusters are redundantly increased and there is an inverse correlation between Let-7 and miR-17/92 clusters in Fhit-expressing cells. Also, a series of in vitro experiments suggests that ELF-1- and/or STAT1-dependent Lin28b regulation is responsible for Let-7 induction in Fhit-expressing cancer cells. Conclusions: Based on the same experimental system proving that Fhit gene has a robust role in suppressing tumor progression and epithelial-mesenchymal transition, our data show that Fhit mediates the negative feedback between Lin28/Let-7 axis and miR-17/-92 miRNA although the physiological relevance of current interesting observation should be further investigated.
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Collections - Biotechnology and Bioengineering > Integrative Biotechnology > 1. Journal Articles
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