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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

PCAF-mediated acetylation of Lin28B increases let-7 biogenesis in lung adenocarcinoma H1299 cells

Authors: Ting-ting Qu, Fei Chen, Jing Wang, Yan-jun Zhang, Mo-bin Cheng, Wen-zheng Sun, Yu-fei Shen, Ye Zhang

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Lin28B and its paralog Lin28A are small RNA binding proteins that have similar inhibitory effects, although they target separate steps in the maturation of let-7 miRNAs in mammalian cells. Because Lin28B participates in the promotion and development of tumors mostly by blocking the let-7 tumor suppressor family members, we sought to explore the associated mechanisms to gain insights into how Lin28B might be decreased in human cancer cells to increase let-7 levels and reverse malignancy.

Results

We demonstrated that the histone acetyltransferase PCAF, via its cold shock domain, directly interacts with and subsequently acetylates Lin28B in lung adenocarcinoma-derived H1299 cells. RT-qPCR assays showed that both let-7a-1 and let-7g were increased in PCAF-transfected H1299 cells. Lin28B is acetylated by ectopic PCAF and translocates from the nucleus to the cytoplasm in H1299 cells.

Conclusions

The effects of acetylated Lin28B on let-7a-1 and let-7g are similar to that of stable knockdown of Lin28B in H1299 cells. The new role of PCAF in mediating Lin28B acetylation and the specific release of its target microRNAs in H1299 cells may shed light on the potential application of let-7 in the clinical treatment of lung cancer patients.
Literature
1.
Moss EG, Lee RC, Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. Elegans and is regulated by the lin-4 RNA. Cell. 1997;88(5):637–46.CrossRefPubMed
2.
Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis Elegans. Nature. 2000;403(6772):901–6.CrossRefPubMed
3.
Slack FJ, Basson M, Liu Z, Ambros V, Horvitz HR, Ruvkun G. The lin-41 RBCC gene acts in the C. Elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell. 2000;5(4):659–69.CrossRefPubMed
4.
5.
6.
Guo Y, Chen Y, Ito H, Watanabe A, Ge X, Kodama T, Aburatani H. Identification and characterization of LIN-28 homolog B (LIN28B) in human hepatocellular carcinoma. Gene. 2006;384:51–61.CrossRefPubMed
7.
Molenaar JJ, Domingo-Fernandez R, Ebus ME, Lindner S, Koster J, Drabek K, Mestdagh P, van Sluis P, Valentijn LJ, van Nes J, et al. LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression. Nat Genet. 2012;44(11):1199–206.CrossRefPubMed
8.
Piskounova E, Polytarchou C, Thornton JE, LaPierre RJ, Pothoulakis C, Hagan JP, Iliopoulos D, Gregory RI. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms. Cell. 2011;147(5):1066–79.CrossRefPubMedPubMedCentral
9.
Wang YC, Chen YL, Yuan RH, Pan HW, Yang WC, Hsu HC, Jeng YM. Lin-28B expression promotes transformation and invasion in human hepatocellular carcinoma. Carcinogenesis. 2010;31(9):1516–22.CrossRefPubMed
10.
Zhou J, Ng SB, Chng WJ. LIN28/LIN28B: an emerging oncogenic driver in cancer stem cells. Int J Biochem Cell Biol. 2013;45(5):973–8.CrossRefPubMed
11.
Heo I, Joo C, Cho J, Ha M, Han J, Kim VN. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol Cell. 2008;32(2):276–84.CrossRefPubMed
12.
Alajez NM, Shi W, Wong D, Lenarduzzi M, Waldron J, Weinreb I, Liu FF. Lin28b promotes head and neck cancer progression via modulation of the insulin-like growth factor survival pathway. Oncotarget. 2012;3(12):1641–52.CrossRefPubMedPubMedCentral
13.
Hu Q, Peng J, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Liu S, Wang H. Lin28B is a novel prognostic marker in gastric adenocarcinoma. Int J Clin Exp Pathol. 2014;7(8):5083–92.PubMedPubMedCentral
14.
King CE, Cuatrecasas M, Castells A, Sepulveda AR, Lee JS, Rustgi AK. LIN28B promotes colon cancer progression and metastasis. Cancer Res. 2011;71(12):4260–8.CrossRefPubMedPubMedCentral
15.
Madison BB, Liu Q, Zhong X, Hahn CM, Lin N, Emmett MJ, Stanger BZ, Lee JS, Rustgi AK. LIN28B promotes growth and tumorigenesis of the intestinal epithelium via Let-7. Genes Dev. 2013;27(20):2233–45.CrossRefPubMedPubMedCentral
16.
Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, et al. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 2009;41(7):843–8.CrossRefPubMedPubMedCentral
17.
Kugel S, Sebastian C, Fitamant J, Ross KN, Saha SK, Jain E, Gladden A, Arora KS, Kato Y, Rivera MN, et al. SIRT6 suppresses pancreatic cancer through control of Lin28b. Cell. 2016;165(6):1401–15.CrossRefPubMedPubMedCentral
18.
Chang TC, Zeitels LR, Hwang HW, Chivukula RR, Wentzel EA, Dews M, Jung J, Gao P, Dang CV, Beer MA, et al. Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferation. Proc Natl Acad Sci U S A. 2009;106(9):3384–9.CrossRefPubMedPubMedCentral
19.
Jiang X, Huang H, Li Z, Li Y, Wang X, Gurbuxani S, Chen P, He C, You D, Zhang S, et al. Blockade of miR-150 maturation by MLL-fusion/MYC/LIN-28 is required for MLL-associated leukemia. Cancer Cell. 2012;22(4):524–35.CrossRefPubMedPubMedCentral
20.
Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009;139(4):693–706.CrossRefPubMedPubMedCentral
21.
Fu M, Wang C, Zhang X, Pestell RG. Acetylation of nuclear receptors in cellular growth and apoptosis. Biochem Pharmacol. 2004;68(6):1199–208.CrossRefPubMed
22.
Mateo F, Vidal-Laliena M, Pujol MJ, Bachs O. Acetylation of cyclin a: a new cell cycle regulatory mechanism. Biochem Soc Trans. 2010;38(Pt 1):83–6.CrossRefPubMed
23.
24.
Lee SH, Cho S, Kim MS, Choi K, Cho JY, Gwak HS, Kim YJ, Yoo H, Lee SH, Park JB, et al. The ubiquitin ligase human TRIM71 regulates let-7 microRNA biogenesis via modulation of Lin28B protein. Biochim Biophys Acta. 2014;1839(5):374–86.CrossRefPubMed
25.
Yin J, Kim TH, Park N, Shin D, Choi HI, Cho S, Park JB, Kim JH. TRIM71 suppresses tumorigenesis via modulation of Lin28B-let-7-HMGA2 signaling. Oncotarget. 2016;7:79854.PubMedPubMedCentral
26.
Wang LX, Wang J, Qu TT, Zhang Y, Shen YF. Reversible acetylation of Lin28 mediated by PCAF and SIRT1. Biochim Biophys Acta. 2014;1843(6):1188–95.CrossRefPubMed
27.
Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33(20):e179.CrossRefPubMedPubMedCentral
28.
Xie R, Wang Y, Nie W, Huang W, Song W, Wang Z, Guan X. Lin28B expression correlates with aggressive clinicopathological characteristics in breast invasive ductal carcinoma. Cancer Biother Radiopharm. 2014;29(5):215–20.CrossRefPubMedPubMedCentral
29.
30.
Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R, Wulczyn FG. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol. 2008;10(8):987–93.CrossRefPubMed
31.
32.
Hikasa H, Sekido Y, Suzuki A. Merlin/NF2-Lin28B-let-7 is a tumor-suppressive pathway that is cell-density dependent and hippo independent. Cell Rep. 2016;14(12):2950–61.CrossRefPubMed
Metadata
Title
PCAF-mediated acetylation of Lin28B increases let-7 biogenesis in lung adenocarcinoma H1299 cells
Authors
Ting-ting Qu
Fei Chen
Jing Wang
Yan-jun Zhang
Mo-bin Cheng
Wen-zheng Sun
Yu-fei Shen
Ye Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3959-0

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