Int J Med Sci 2021; 18(3):706-714. doi:10.7150/ijms.51429 This issue

Research Paper

Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR

Hae-Jung Chae1, Jong Bae Seo1,2, Sung-Hak Kim3, Young-Jun Jeon4✉, Sung-Suk Suh1,2✉

1. Department of Biosciences, Mokpo National University, Joennam 58554, South Korea
2. Department of Biomedicine, Health & Life Convergence Science, BK21 Four, Mokpo National University, Joennam 58554, South Korea
3. Lab of Animal Molecular Biochemistry, Chonnam National University, Gwangju, 61186, Republic of Korea.
4. Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, South Korea.

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Chae HJ, Seo JB, Kim SH, Jeon YJ, Suh SS. Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR. Int J Med Sci 2021; 18(3):706-714. doi:10.7150/ijms.51429. Available from

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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.

Keywords: Fhit, miRNAs, tumor suppressor, Let-7, Lin28b