Hsa_Circ_0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

Zheying Zhang; Wenyan Fan; Qingzu Gao; Yifei Han; Jingyu Ma; Wuji Gao; Yuhan Hu; Huifang Zhu; Rui Yang; Haijun Wang; Baoshun Du; Zuoyang Zhang; Jiateng Zhong

doi:10.1016/j.jgg.2022.07.006

Volume 50 Issue 3

Mar. 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(3): 192-203

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Hsa_Circ_0000826 inhibits the proliferation of colorectal cancer by targeting AUF1

doi: 10.1016/j.jgg.2022.07.006

a. Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China;
b. Department of Microscopic Morphology Laboratory, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China;
c. Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, China;
d. School of Life Science and Technology, Xinxiang Medical University, Xinxiang, Henan 453003, China;
e. Second Department of Neurosurgery, Xinxiang Central Hospital, Xinxiang, Henan 453003, China;
f. Department of Pathology, Anhui Medical University, Hefei, Anhui 230032, China

Funds:

This work is supported by the National Natural Science Foundation of China (Grant Nos. 81802470, 31800658, and U1804173), the Department of Science and Technology, Henan Province (Grant Nos. 212102310621 and 192102310362), Joint construction project of Henan Medical Science and technology research plan (No. LHGJ20210910), and the Xinxiang Medical University research funding (Grant No. XYBSKYZZ201632).We would like to thank manager Zhu of the Henan Writegene Biotechnology CO., LTD for his technical guidance.

Received Date: 2022-06-20
Accepted Date: 2022-07-28
Rev Recd Date: 2022-07-25
Publish Date: 2022-08-05

Abstract

Abstract

Many circular RNAs (circRNAs) are reported to be abnormally expressed during the progression of various tumors, and these circRNAs can be used as anti-tumor targets. Therefore, it is important to identify circRNAs that can be used effectively for the clinical diagnosis and treatment of colorectal cancer (CRC). Here, we report that hsa_Circ_0000826 (Circ_0000826), a circRNA with significantly reduced expression level in CRC tissues, is associated with a poor prognosis in patients. The silencing of Circ_0000826 promotes the proliferation of CRC cells. Conversely, the overexpression of Circ_0000826 restricted CRC cell proliferation both in vitro and in vivo. Furthermore, Circ_0000826 could target AU-rich element RNA-binding protein 1 (AUF1). AUF1, known as heterogeneous nuclear ribonucleoprotein D (hnRNP D), could bind to the c-MYC 3′-UTR and promote c-MYC expression. When Circ_0000826 binds to AUF1, it competitively inhibits the binding of AUF1 to the c-MYC 3′-UTR, which inhibits the c-MYC expression and cell proliferation. These results provide novel insights into the functional mechanism of Circ_0000826 action in CRC progression and indicate its potential use as a therapeutic target in CRC.
- Colorectal cancer,
- Hsa_Circ_0000826,
- AUF1,
- Proliferation,
- CircRNA

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References(38)

References

[1]	Agostini, F, Zanzoni, A, Klus, P, Marchese, D, Cirillo, D, and Tartaglia, G G. 2013. catRAPID omics: a web server for large-scale prediction of protein-RNA interactions. Bioinformatics. 29, 2928-2930.
[2]	Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S. 2014. circRNA biogenesis competes with pre-mRNA splicing. Mol. Cell. 56, 55-66.
[3]	Bai, R, Li, D, Shi, Z, Fang, X, Ge, W, and Zheng, S. 2013. Clinical significance of Ankyrin repeat domain 12 expression in colorectal cancer. J. Exp. Clin. Cancer Res. 32, 35.
[4]	Chen, S, Li, T, Zhao, Q, Xiao, B, and Guo, J. 2017. Using circular RNA hsa_circ_0000190 as a new biomarker in the diagnosis of gastric cancer. Clin. Chim. Acta. 466, 167-171.
[5]	Du, W W, Yang, W, Liu, E, Yang, Z, Dhaliwal, P, and Yang, B B. 2016. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res. 44, 2846-2858.
[6]	Guo J, Gao J, Li Z, Gong Y, Man X, Jin J, Wu H. 2013. Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo. Cancer Lett. 339,185-194.
[7]	Geng, Y., Zhang, L., Xu, M., Sheng, W., Dong, A., Cao, J., Cao, J., 2015. The expression and significance of hnRNPD in esophageal squamous cell carcinoma cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 31, 1659–1663.
[8]	Geuens, T, Bouhy, D, and Timmerman, V. 2016. The hnRNP family: insights into their role in health and disease. Hum. Genet. 135, 851-867.
[9]	Goodall, G J, and Wickramasinghe, V O. 2020. RNA in cancer. Nat. Rev. Cancer.
[10]	Huang A, Zheng H, Wu Z, Chen M, Huang Y. 2020. Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics 10, 3503-3517.
[11]	Kumar M, Matta A, Masui O, Srivastava G, Kaur J, Thakar A, Shukla NK, RoyChoudhury A, Sharma M, Walfish PG, et al. 2015. Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor prognosis and interactome analysis reveals its novel binding partners in oral cancer. J. Transl. Med. 13, 285.
[12]	Lee KH, Kim SH, Kim HJ, Kim W, Lee HR, Jung Y, Choi JH, Hong KY, Jang SK, Kim KT. 2014. AUF1 contributes to Cryptochrome1 mRNA degradation and rhythmic translation. Nucleic Acids Res. 42, 3590-3606.
[13]	Liao, B, Hu, Y, and Brewer, G. 2007. Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation. Nat. Struct. Mol. Biol. 14, 511-518.
[14]	Memczak, S, Papavasileiou, P, Peters, O, and Rajewsky, N. 2015. Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One. 10, e0141214.
[15]	Panda AC, Abdelmohsen K, Yoon JH, Martindale JL, Yang X, Curtis J, Mercken EM, Chenette DM, Zhang Y, Schneider RJ, et al. 2014. RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels. Mol. Cell Biol. 34, 3106-3119.
[16]	Panda, A.C., Gorospe, M., 2018. Detection and analysis of Circular RNAs by RT-PCR. Bio. Protoc. 8, e2775.
[17]	Pathan M, Keerthikumar S, Ang CS, Gangoda L, Quek CY, Williamson NA, Mouradov D, Sieber OM, Simpson RJ, Salim A, et al. 2015. FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics. 15, 2597-2601.
[18]	Patop IL, Wust S, Kadener S. 2019. Past, present, and future of circRNAs. EMBO J. 38:e100836.
[19]	Piwecka M, Glazar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, Filipchyk A, Klironomos F, Cerda Jara CA, Fenske P, et al. 2017. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 357.
[20]	Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM. 2004. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 6, 1-6. https://doi.org/10.1016/s1476-5586(04)80047-2.
[21]	Shaul YD, Yuan B, Thiru P, Nutter-Upham A, McCallum S, Lanzkron C, Bell GW, Sabatini DM. 2016. MERAV: a tool for comparing gene expression across human tissues and cell types. Nucleic Acids Res. 44, D560-D566.
[22]	Shi, L, Tao, C, Tang, Y, Xia, Y, Li, X, and Wang, X. 2020. Hypoxia-induced hsa_circ_0000826 is linked to liver metastasis of colorectal cancer. J. Clin. Lab. Anal. e23405.
[23]	Siegel RL, Miller KD, Fuchs HE, Jemal A. 2021. Cancer statistics. CA A Cancer J. Clin. 71,7-33.
[24]	Tian XY, Li J, Liu TH, Li DN, Wang JJ, Zhang H, Deng ZL, Chen FJ, Cai JP. 2020. The overexpression of AUF1 in colorectal cancer predicts a poor prognosis and promotes cancer progression by activating ERK and AKT pathways. Cancer Med. 9:8612-8623.
[25]	Thul PJ, Akesson L, Wiking M, Mahdessian D, Geladaki A, Ait Blal H, Alm T, Asplund A, Bjork L, Breckels LM, et al. 2017. A subcellular map of the human proteome. Science, 356, eaal3321.
[26]	Tsitsipatis D, Grammatikakis I, Driscoll RK, Yang X, Abdelmohsen K, Harris SC, Yang JH, Herman AB, Chang MW, Munk R, et al. 2021. AUF1 ligand circPCNX reduces cell proliferation by competing with p21 mRNA to increase p21 production. Nucleic Acids Res. 49:1631-1646.
[27]	Uhlen M, Zhang C, Lee S, Sjostedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, et al. 2017. A pathology atlas of the human cancer transcriptome. Science, 357, eaan2507.
[28]	Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson A, Kampf C, Sjostedt E, Asplund A, et al. 2015 Proteomics. Tissue-based map of the human proteome. Science. 347, 1260419.
[29]	Wang, Z, Wang, L, Hu, J, Fan, R, Zhou, J, Wang, L, Zhong J. 2015. RARRES3 suppressed metastasis through suppression of MTDH to regulate epithelial-mesenchymal transition in colorectal cancer. Am J Cancer Res. 5, 1988-1999.
[30]	Weng W, Wei Q, Toden S, Yoshida K, Nagasaka T, Fujiwara T, Cai S, Qin H, Ma Y, Goel A. 2017. Circular RNA ciRS-7-A promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin. Cancer Res. 23, 3918-3928.
[31]	White, E.J., Matsangos, A.E., Wilson, G.M., 2017. AUF1 regulation of coding and noncoding RNA. Wiley Interdiscip. Rev. RNA 8.
[32]	Xiao ZD, Han L, Lee H, Zhuang L, Zhang Y, Baddour J, Nagrath D, Wood CG, Gu J, Wu X, et al. 2017. Energy stress-induced lncRNA FILNC1 represses c-Myc-mediated energy metabolism and inhibits renal tumor development. Nat. Commun. 8, 783.
[33]	Xu, L, Zhang, M, Zheng, X, Yi, P, Lan, C, and Xu, M. 2017. The circular RNA ciRS-7 (Cdr1as) acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 143, 17-27.
[34]	Xue M, Chen LY, Wang WJ, Su TT, Shi LH, Wang L, Zhang W, Si JM, Wang LJ, Chen SJ. 2018. HOTAIR induces the ubiquitination of Runx3 by interacting with Mex3b and enhances the invasion of gastric cancer cells. Gastric Cancer. 21, 756-764.
[35]	Yoon JH, De S, Srikantan S, Abdelmohsen K, Grammatikakis I, Kim J, Kim KM, Noh JH, White EJ, Martindale JL, et al. 2014. PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nat. Commun. 5:5248.
[36]	Zhang A, Yeung PL, Li CW, Tsai SC, Dinh GK, Wu X, Li H, Chen JD. 2004. Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators. J. Biol. Chem. 279, 33799-33805.
[37]	Zhang Z, Song N, Wang Y, Zhong J, Gu T, Yang L, Shen X, Li Y, Yang X, Liu X, et al. 2019. Analysis of differentially expressed circular RNAs for the identification of a coexpression RNA network and signature in colorectal cancer. J. Cell. Biochem. 120, 6409-6419.
[38]	Zhou WY, Cai ZR, Liu J, Wang DS, Ju HQ, Xu RH. 2020. Circular RNA: metabolism, functions and interactions with proteins. Mol. Cancer 19, 172.