Competing Endogenous RNA of Snail and Zeb1 UTR in Therapeutic Resistance of Colorectal Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Sep 10

PMID 34502497

Citations 6

Authors

Nam Hee Kim

Sang Hyun Song

Yun Hee Choi

Kyu Ho Hwang

Jun Seop Yun

Hyeeun Song

So Young Cha

Sue Bean Cho

Inhan Lee

Hyun Sil Kim

Jong In Yook

Affiliations

Soon will be listed here.

Abstract

The epithelial-mesenchymal transition (EMT) comprises an important biological mechanism not only for cancer progression but also in the therapeutic resistance of cancer cells. While the importance of the protein abundance of EMT-inducers, such as Snail (SNAI1) and Zeb1 (ZEB1), during EMT progression is clear, the reciprocal interactions between the untranslated regions (UTRs) of EMT-inducers via a competing endogenous RNA (ceRNA) network have received little attention. In this study, we found a synchronized transcript abundance of Snail and Zeb1 mediated by a non-coding RNA network in colorectal cancer (CRC). Importantly, the -regulatory ceRNA network in the UTRs of EMT inducers is mediated by competition between tumor suppressive miRNA-34 (miR-34) and miRNA-200 (miR-200). Furthermore, the ceRNA network consisting of the UTRs of EMT inducers and tumor suppressive miRs is functional in the EMT phenotype and therapeutic resistance of colon cancer. In The Cancer Genome Atlas (TCGA) samples, we also found genome-wide ceRNA gene sets regulated by miR-34a and miR-200 in colorectal cancer. These results indicate that the ceRNA networks regulated by the reciprocal interaction between EMT gene UTRs and tumor suppressive miRs are functional in CRC progression and therapeutic resistance.

Citing Articles

New Perspectives in Colorectal Cancers Treatment, the Role of MicroRNAs.

Belova V, Spirina L, Avgustinovich A, Afanasev S, Volkov M, Azovsky D Curr Drug Targets. 2024; 25(11):715-723.

PMID: 39051587 DOI: 10.2174/0113894501304351240703113651.

LINC01117 inhibits invasion and migration of lung adenocarcinoma through influencing EMT process.

Liu L, Ren W, Du L, Xu K, Zhou Y PLoS One. 2023; 18(6):e0287926.

PMID: 37384755 PMC: 10310029. DOI: 10.1371/journal.pone.0287926.

Boolean modeling of mechanosensitive epithelial to mesenchymal transition and its reversal.

Sullivan E, Harris M, Bhatnagar A, Guberman E, Zonfa I, Regan E iScience. 2023; 26(4):106321.

PMID: 36968076 PMC: 10030917. DOI: 10.1016/j.isci.2023.106321.

Identification of Key MicroRNAs and Genes between Colorectal Adenoma and Colorectal Cancer via Deep Learning on GEO Databases and Bioinformatics.

Zhang X, Jin M, Liu F, Qu H, Chen C Contrast Media Mol Imaging. 2023; 2023:6457152.

PMID: 36793496 PMC: 9922557. DOI: 10.1155/2023/6457152.

Current Progress of EMT: A New Direction of Targeted Therapy for Colorectal Cancer with Invasion and Metastasis.

Tan Z, Sun W, Li Y, Jiao X, Zhu M, Zhang J Biomolecules. 2022; 12(12).

PMID: 36551152 PMC: 9775097. DOI: 10.3390/biom12121723.

References

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

Ju S, Chiou S, Su Y . Maintenance of the stemness in CD44(+) HCT-15 and HCT-116 human colon cancer cells requires miR-203 suppression. Stem Cell Res. 2013; 12(1):86-100. DOI: 10.1016/j.scr.2013.09.011. View

Ahn Y, Gibbons D, Chakravarti D, Creighton C, Rizvi Z, Adams H . ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression. J Clin Invest. 2012; 122(9):3170-83. PMC: 3428095. DOI: 10.1172/JCI63608. View

Perdigao-Henriques R, Petrocca F, Altschuler G, Thomas M, Le M, Tan S . miR-200 promotes the mesenchymal to epithelial transition by suppressing multiple members of the Zeb2 and Snail1 transcriptional repressor complexes. Oncogene. 2015; 35(2):158-72. DOI: 10.1038/onc.2015.69. View

Spaderna S, Brabletz T, Opitz O . The miR-200 family: central player for gain and loss of the epithelial phenotype. Gastroenterology. 2009; 136(5):1835-7. DOI: 10.1053/j.gastro.2009.03.009. View

Kim N, Kim H, Li X, Lee I, Choi H, Kang S . A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol. 2011; 195(3):417-33. PMC: 3206336. DOI: 10.1083/jcb.201103097. View

Liu Y, Yu C, Wu Y, Sun X, Su Q, You C . CD44 fibroblasts increases breast cancer cell survival and drug resistance via IGF2BP3-CD44-IGF2 signalling. J Cell Mol Med. 2017; 21(9):1979-1988. PMC: 5571562. DOI: 10.1111/jcmm.13118. View

Camarda R, Zhou A, Kohnz R, Balakrishnan S, Mahieu C, Anderton B . Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer. Nat Med. 2016; 22(4):427-32. PMC: 4892846. DOI: 10.1038/nm.4055. View

Chu P, Clanton D, Snipas T, Lee J, Mitchell E, Nguyen M . Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer. 2008; 124(6):1312-21. DOI: 10.1002/ijc.24061. View

10.

Mavrakis K, Wendel H . TargetScreen: an unbiased approach to identify functionally important microRNA targets. Cell Cycle. 2010; 9(11):2080-4. DOI: 10.4161/cc.9.11.11807. View

11.

Mani S, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N . Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A. 2007; 104(24):10069-74. PMC: 1891217. DOI: 10.1073/pnas.0703900104. View

12.

Vincent T, Neve E, Johnson J, Kukalev A, Rojo F, Albanell J . A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat Cell Biol. 2009; 11(8):943-50. PMC: 3769970. DOI: 10.1038/ncb1905. View

13.

In Yook J, Li X, Ota I, Hu C, Kim H, Kim N . A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006; 8(12):1398-406. DOI: 10.1038/ncb1508. View

14.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

15.

Sanchez-Tillo E, Lazaro A, Torrent R, Cuatrecasas M, Vaquero E, Castells A . ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1. Oncogene. 2010; 29(24):3490-500. DOI: 10.1038/onc.2010.102. View

16.

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

17.

Lee I, Ajay S, In Yook J, Kim H, Hong S, Kim N . New class of microRNA targets containing simultaneous 5'-UTR and 3'-UTR interaction sites. Genome Res. 2009; 19(7):1175-83. PMC: 2704433. DOI: 10.1101/gr.089367.108. View

18.

Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4):275-84. DOI: 10.1038/nrc1590. View

19.

Guo H, Ingolia N, Weissman J, Bartel D . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010; 466(7308):835-40. PMC: 2990499. DOI: 10.1038/nature09267. View

20.

Lee Y, Kim N, Cho E, Yang J, Cha Y, Kang H . Dishevelled has a YAP nuclear export function in a tumor suppressor context-dependent manner. Nat Commun. 2018; 9(1):2301. PMC: 5997650. DOI: 10.1038/s41467-018-04757-w. View