TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling
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Jinlong Yin1,3, Tae-Hoon Kim3, Nayun Park1,2, Daye Shin1,2, Hae In Choi1,2, Sungchan Cho4, Jong Bae Park1,3, Jong Heon Kim1,2
1Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi, Korea
2Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Korea
3Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi, Korea
4Anticancer Agent Research Center, Korea Research Institute of Bioscience & Biotechnology, Ochang, Korea
Jong Heon Kim, email: email@example.com
Jong Bae Park, email: firstname.lastname@example.org
Keywords: TRIM71, Lin28B, let-7, HMGA2, tumorigenesis
Received: September 16, 2016 Accepted: October 14, 2016 Published: November 03, 2016
TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion. Conversely, overexpression of wild-type TRIM71 in non-small cell lung carcinoma (NSCLC) cells in which Lin28B-let-7-HMGA2 signaling was conserved decreased both cancer cell phenotypes. More importantly, overexpression of an ubiquitin transfer activity-deficient TRIM71 mutant in NSCLC cells had no effect on proliferation or invasion, regardless of the conservation status of Lin28B-let-7-HMGA2 signaling. The tumorigenic inhibitory action of TRIM71 was antagonized by overexpression of the TRIM71 downstream targets, Lin28B and HMGA2. Furthermore, a bioinformatics analysis revealed that TRIM71 expression was downregulated in various types of cancer tissue from patients. Taken together, these data indicate that TRIM71 acts through post-transcriptional repression of Lin28B and subsequent modulation of let-7-HMGA2 signaling during tumorigenesis to potentially function as a tumor suppressor.
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