MiR-493 Induction During Carcinogenesis Blocks Metastatic Settlement of Colon Cancer Cells in Liver

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2012 Mar 1

PMID 22373578

Citations 42

Authors

Koji Okamoto

Tatsuya Ishiguro

Yutaka Midorikawa

Hirokazu Ohata

Masashi Izumiya

Naoto Tsuchiya

Ai Sato

Hiroaki Sakai

Hitoshi Nakagama

Affiliations

Soon will be listed here.

Abstract

Liver metastasis is a major lethal complication associated with colon cancer, and post-intravasation steps of the metastasis are important for its clinical intervention. In order to identify inhibitory microRNAs (miRNAs) for these steps, we performed 'dropout' screens of a miRNA library in a mouse model of liver metastasis. Functional analyses showed that miR-493 and to a lesser extent miR-493(*) were capable of inhibiting liver metastasis. miR-493 inhibited retention of metastasized cells in liver parenchyma and induced their cell death. IGF1R was identified as a direct target of miR-493, and its inhibition partially phenocopied the anti-metastatic effects. High levels of miR-493 and miR-493(*), but not pri-miR-493, in primary colon cancer were inversely related to the presence of liver metastasis, and attributed to an increase of miR-493 expression during carcinogenesis. We propose that, in a subset of colon cancer, upregulation of miR-493 during carcinogenesis prevents liver metastasis via the induction of cell death of metastasized cells.

Citing Articles

MicroRNAs Influence the Migratory Ability of Human Umbilical Vein Endothelial Cells.

Wang Z, Zeng Z, Starkuviene V, Erfle H, Kan K, Zhang J Genes (Basel). 2022; 13(4).

PMID: 35456446 PMC: 9029696. DOI: 10.3390/genes13040640.

MicroRNA as an Important Target for Anticancer Drug Development.

Fu Z, Wang L, Li S, Chen F, Au-Yeung K, Shi C Front Pharmacol. 2021; 12:736323.

PMID: 34512363 PMC: 8425594. DOI: 10.3389/fphar.2021.736323.

miR-493 by regulating of c-Jun targets Wnt5a/PD-L1-inducing esophageal cancer cell development.

Bian W, Li Y, Zhu H, Gao S, Niu R, Wang C Thorac Cancer. 2021; 12(10):1579-1588.

PMID: 33793074 PMC: 8107036. DOI: 10.1111/1759-7714.13950.

microRNAs and Corresponding Targets Involved in Metastasis of Colorectal Cancer in Preclinical Models.

Weidle U, Brinkmann U, Auslaender S Cancer Genomics Proteomics. 2020; 17(5):453-468.

PMID: 32859626 PMC: 7472456. DOI: 10.21873/cgp.20204.

MicroRNA-493-5p-mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion.

Yasukawa K, Liew L, Hagiwara K, Hironaka-Mitsuhashi A, Qin X, Furutani Y Cancer Sci. 2019; 111(3):869-880.

PMID: 31883160 PMC: 7060481. DOI: 10.1111/cas.14292.

References

Iguchi H, Kosaka N, Ochiya T . Versatile applications of microRNA in anti-cancer drug discovery: from therapeutics to biomarkers. Curr Drug Discov Technol. 2010; 7(2):95-105. DOI: 10.2174/157016310793180648. View

Hess K, Varadhachary G, Taylor S, Wei W, Raber M, Lenzi R . Metastatic patterns in adenocarcinoma. Cancer. 2006; 106(7):1624-33. DOI: 10.1002/cncr.21778. View

Schlabach M, Luo J, Solimini N, Hu G, Xu Q, Li M . Cancer proliferation gene discovery through functional genomics. Science. 2008; 319(5863):620-4. PMC: 2981870. DOI: 10.1126/science.1149200. View

Okamoto K, Kashima K, Pereg Y, Ishida M, Yamazaki S, Nota A . DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation. Mol Cell Biol. 2005; 25(21):9608-20. PMC: 1265801. DOI: 10.1128/MCB.25.21.9608-9620.2005. View

Park S, Gaur A, Lengyel E, Peter M . The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008; 22(7):894-907. PMC: 2279201. DOI: 10.1101/gad.1640608. View

Chitnis M, Yuen J, Protheroe A, Pollak M, Macaulay V . The type 1 insulin-like growth factor receptor pathway. Clin Cancer Res. 2008; 14(20):6364-70. DOI: 10.1158/1078-0432.CCR-07-4879. View

Miyamoto S, Nakamura M, Shitara K, Nakamura K, Ohki Y, Ishii G . Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers. Clin Cancer Res. 2005; 11(9):3494-502. DOI: 10.1158/1078-0432.CCR-04-1701. View

Zhang X, Wan G, Berger F, He X, Lu X . The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell. 2011; 41(4):371-83. PMC: 3114434. DOI: 10.1016/j.molcel.2011.01.020. View

Hamada K, Monnai M, Kawai K, Nishime C, Kito C, Miyazaki N . Liver metastasis models of colon cancer for evaluation of drug efficacy using NOD/Shi-scid IL2Rgammanull (NOG) mice. Int J Oncol. 2007; 32(1):153-9. View

10.

Ewing G, Goff L . The insulin-like growth factor signaling pathway as a target for treatment of colorectal carcinoma. Clin Colorectal Cancer. 2010; 9(4):219-23. DOI: 10.3816/CCC.2010.n.032. View

11.

Chambers A, Groom A, MacDonald I . Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002; 2(8):563-72. DOI: 10.1038/nrc865. View

12.

Wang J, Yang M, Hoffman R . Visualizing portal vein metastatic trafficking to the liver with green fluorescent protein-expressing tumor cells. Anticancer Res. 2005; 24(6):3699-702. View

13.

Gupta G, Massague J . Cancer metastasis: building a framework. Cell. 2006; 127(4):679-95. DOI: 10.1016/j.cell.2006.11.001. View

14.

Petrocca F, Lieberman J . Promise and challenge of RNA interference-based therapy for cancer. J Clin Oncol. 2010; 29(6):747-54. DOI: 10.1200/JCO.2009.27.6287. View

15.

Dong Y, Wu W, Wu C, Sung J, Yu J, Ng S . MicroRNA dysregulation in colorectal cancer: a clinical perspective. Br J Cancer. 2011; 104(6):893-8. PMC: 3065287. DOI: 10.1038/bjc.2011.57. View

16.

Iorio M, Croce C . MicroRNAs in cancer: small molecules with a huge impact. J Clin Oncol. 2009; 27(34):5848-56. PMC: 2793003. DOI: 10.1200/JCO.2009.24.0317. View

17.

le Sage C, Nagel R, Egan D, Schrier M, Mesman E, Mangiola A . Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007; 26(15):3699-708. PMC: 1949005. DOI: 10.1038/sj.emboj.7601790. View

18.

Voorhoeve P, le Sage C, Schrier M, Gillis A, Stoop H, Nagel R . A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006; 124(6):1169-81. DOI: 10.1016/j.cell.2006.02.037. View

19.

Suzuki H, Miyazono K . Emerging complexity of microRNA generation cascades. J Biochem. 2010; 149(1):15-25. DOI: 10.1093/jb/mvq113. View

20.

Ventura A, Jacks T . MicroRNAs and cancer: short RNAs go a long way. Cell. 2009; 136(4):586-91. PMC: 3910108. DOI: 10.1016/j.cell.2009.02.005. View