Unique MiRNA Expression Profile in MSI- and EMAST-Unstable Sporadic Colon Cancer

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2024 Aug 29

PMID 39202367

Authors

Sonja Marinovic

Kristina Vukovic Derfi

Anita Skrtic

Mirko Poljak

Sanja Kapitanovic

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are critical post-transcriptional gene regulators and their involvement in sporadic colon cancer (CRC) tumorigenesis has been confirmed. In this study we investigated differences in miRNA expression in microsatellite stable (MSS/EMAST-S), microsatellite unstable marked by high elevated microsatellite alterations at selected tetranucleotide repeats (MSS/EMAST-H), and high microsatellite unstable (MSI-H/EMAST-H) tumor subgroups as well as in tumors with different clinicopathologic characteristics. An RT-qPCR analysis of miRNA expression was carried out on 45 colon cancer and adjacent normal tissue samples (15 of each group). Overall, we found three differentially expressed miRNAs between the subgroups. miR-92a-3p and miR-224-5p were significantly downregulated in MSI-H/EMAST-H tumors in comparison to other subgroups. miR-518c-3p was significantly upregulated in MSS/EMAST-H tumors in comparison to stable and highly unstable tumors. Furthermore, we showed that miR-143-3p and miR-145-5p were downregulated in tumors in comparison to normal tissues in all subgroups. In addition, we showed overexpression of miR-125b-5p in well-differentiated tumors and miR-451a in less advanced tumors. This is the first report on differences in miRNA expression profiles between MSS/EMAST-S, MSS/EMAST-H, and MSI-H/EMAST-H colorectal cancers. Our findings indicate that the miRNA expression signatures differ in CRC subgroups based on their instability status.

References

Murphy K, Zhang S, Geiger T, Hafez M, Bacher J, Berg K . Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn. 2006; 8(3):305-11. PMC: 1867601. DOI: 10.2353/jmoldx.2006.050092. View

Fridrichova I, Zmetakova I . MicroRNAs Contribute to Breast Cancer Invasiveness. Cells. 2019; 8(11). PMC: 6912645. DOI: 10.3390/cells8111361. View

Pellatt A, Mullany L, Herrick J, Sakoda L, Wolff R, Samowitz W . The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs. J Transl Med. 2018; 16(1):191. PMC: 6038278. DOI: 10.1186/s12967-018-1566-8. View

He L, He X, Lowe S, Hannon G . microRNAs join the p53 network--another piece in the tumour-suppression puzzle. Nat Rev Cancer. 2007; 7(11):819-22. PMC: 4053212. DOI: 10.1038/nrc2232. View

Qin M, Chai X, Huang H, Feng G, Li X, Zhang J . let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1. BMC Urol. 2019; 19(1):53. PMC: 6567622. DOI: 10.1186/s12894-019-0485-1. View

Yang H, Ren J, Bai Y, Jiang J, Xiao S . MicroRNA-518-3p suppresses cell proliferation, invasiveness, and migration in colorectal cancer via targeting . Biochem Cell Biol. 2020; 98(5):575-582. DOI: 10.1139/bcb-2019-0442. View

Calin G, Dumitru C, Shimizu M, Bichi R, Zupo S, Noch E . Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002; 99(24):15524-9. PMC: 137750. DOI: 10.1073/pnas.242606799. View

Ding L, Lan Z, Xiong X, Ao H, Feng Y, Gu H . The Dual Role of MicroRNAs in Colorectal Cancer Progression. Int J Mol Sci. 2018; 19(9). PMC: 6164944. DOI: 10.3390/ijms19092791. View

Banzhaf-Strathmann J, Edbauer D . Good guy or bad guy: the opposing roles of microRNA 125b in cancer. Cell Commun Signal. 2014; 12:30. PMC: 4011766. DOI: 10.1186/1478-811X-12-30. View

10.

Catela Ivkovic T, Voss G, Cornella H, Ceder Y . microRNAs as cancer therapeutics: A step closer to clinical application. Cancer Lett. 2017; 407:113-122. DOI: 10.1016/j.canlet.2017.04.007. View

11.

Wang H, Wang X, Xu L, Zhang J, Cao H . Analysis of the transcriptomic features of microsatellite instability subtype colon cancer. BMC Cancer. 2019; 19(1):605. PMC: 6585086. DOI: 10.1186/s12885-019-5802-2. View

12.

Marinovic S, Vukovic K, Skrtic A, Poljak M, Petek S, Petek L . Epidermal growth factor receptor intron 1 polymorphism and microsatellite instability in sporadic colorectal cancer. Oncol Lett. 2021; 21(2):131. PMC: 7798105. DOI: 10.3892/ol.2020.12392. View

13.

Cenariu D, Zimta A, Munteanu R, Onaciu A, Moldovan C, Jurj A . Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene. Pharmaceutics. 2021; 13(5). PMC: 8148199. DOI: 10.3390/pharmaceutics13050664. View

14.

Tay Y, Tan S, Karreth F, Lieberman J, Pandolfi P . Characterization of dual PTEN and p53-targeting microRNAs identifies microRNA-638/Dnm2 as a two-hit oncogenic locus. Cell Rep. 2014; 8(3):714-22. PMC: 4128194. DOI: 10.1016/j.celrep.2014.06.064. View

15.

Li Y, Zeng C, Hu J, Pan Y, Shan Y, Liu B . Long non-coding RNA-SNHG7 acts as a target of miR-34a to increase GALNT7 level and regulate PI3K/Akt/mTOR pathway in colorectal cancer progression. J Hematol Oncol. 2018; 11(1):89. PMC: 6029165. DOI: 10.1186/s13045-018-0632-2. View

16.

Gironella M, Seux M, Xie M, Cano C, Tomasini R, Gommeaux J . Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A. 2007; 104(41):16170-5. PMC: 2042180. DOI: 10.1073/pnas.0703942104. View

17.

Zhang G, Zhou H, Xiao H, Liu Z, Tian H, Zhou T . MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN. Dig Dis Sci. 2013; 59(1):98-107. DOI: 10.1007/s10620-013-2858-8. View

18.

Zhu J, Xu Y, Liu S, Qiao L, Sun J, Zhao Q . MicroRNAs Associated With Colon Cancer: New Potential Prognostic Markers and Targets for Therapy. Front Bioeng Biotechnol. 2020; 8:176. PMC: 7075808. DOI: 10.3389/fbioe.2020.00176. View

19.

Calin G, Sevignani C, Dumitru C, Hyslop T, Noch E, Yendamuri S . Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004; 101(9):2999-3004. PMC: 365734. DOI: 10.1073/pnas.0307323101. View

20.

Veigl M, Kasturi L, Olechnowicz J, Ma A, Lutterbaugh J, Periyasamy S . Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A. 1998; 95(15):8698-702. PMC: 21139. DOI: 10.1073/pnas.95.15.8698. View