MicroRNA-193b Represses Cell Proliferation and Regulates Cyclin D1 in Melanoma

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 2010 Mar 23

PMID 20304954

Citations 114

Authors

Jiamin Chen

Harriet E Feilotter

Genevieve C Pare

Xiao Zhang

Joshua G W Pemberton

Cherif Garady

Dulcie Lai

Xiaolong Yang

Victor A Tron

Affiliations

Soon will be listed here.

Abstract

Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. To better understand the role of microRNAs (miRNAs) in melanoma, the expression of 470 miRNAs was profiled in tissue samples from benign nevi and metastatic melanomas. We identified 31 miRNAs that were differentially expressed (13 up-regulated and 18 down-regulated) in metastatic melanomas relative to benign nevi. Notably, miR-193b was significantly down-regulated in the melanoma tissues examined. To understand the role of miR-193b in melanoma, functional studies were undertaken. Overexpression of miR-193b in melanoma cell lines repressed cell proliferation. Gene expression profiling identified 314 genes down-regulated by overexpression of miR-193b in Malme-3M cells. Eighteen of these down-regulated genes, including cyclin D1 (CCND1), were also identified as putative miR-193b targets by TargetScan. Overexpression of miR-193b in Malme-3M cells down-regulated CCND1 mRNA and protein by > or = 50%. A luciferase reporter assay confirmed that miR-193b directly regulates CCND1 by binding to the 3'untranslated region of CCND1 mRNA. These studies indicate that miR-193b represses cell proliferation and regulates CCND1 expression and suggest that dysregulation of miR-193b may play an important role in melanoma development.

Citing Articles

miR-193b-3p suppresses lung cancer cell migration and invasion through PRNP targeting.

Ho H, Lin S, Chiang C, Lin C, Liu C, Yeh Y J Biomed Sci. 2025; 32(1):28.

PMID: 39972491 PMC: 11841292. DOI: 10.1186/s12929-025-01121-1.

Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis.

Rafiepoor H, Ghorbankhanloo A, Soleimani Dorcheh S, Angouraj Taghavi E, Ghanadan A, Shirkoohi R J Cell Mol Med. 2025; 29(2):e70367.

PMID: 39823244 PMC: 11740884. DOI: 10.1111/jcmm.70367.

Identification of exosomal microRNAs and related hub genes associated with imatinib resistance in chronic myeloid leukemia.

Karabay A, Ozkan T, Karadag Gurel A, Koc A, Hekmatshoar Y, Sunguroglu A Naunyn Schmiedebergs Arch Pharmacol. 2024; 397(12):9701-9721.

PMID: 38916832 PMC: 11582232. DOI: 10.1007/s00210-024-03198-1.

Epigenetic Downregulation of Hsa-miR-193b-3p Increases Cyclin D1 Expression Level and Cell Proliferation in Human Meningiomas.

Kober P, Mossakowska B, Rusetska N, Baluszek S, Grecka E, Konopinski R Int J Mol Sci. 2023; 24(17).

PMID: 37686289 PMC: 10487813. DOI: 10.3390/ijms241713483.

Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition.

Hu Q, Huang T Int J Mol Sci. 2023; 24(10).

PMID: 37240281 PMC: 10219488. DOI: 10.3390/ijms24108939.

References

Wu W, Lin Z, Zhuang Z, Liang X . Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2008; 18(1):50-5. DOI: 10.1097/CEJ.0b013e328305a07a. View

Cimmino A, Calin G, Fabbri M, Iorio M, Ferracin M, Shimizu M . miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102(39):13944-9. PMC: 1236577. DOI: 10.1073/pnas.0506654102. View

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

Schultz J, Lorenz P, Gross G, Ibrahim S, Kunz M . MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res. 2008; 18(5):549-57. DOI: 10.1038/cr.2008.45. View

Johnson S, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A . RAS is regulated by the let-7 microRNA family. Cell. 2005; 120(5):635-47. DOI: 10.1016/j.cell.2005.01.014. View

Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo Y . MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res. 2008; 18(3):350-9. DOI: 10.1038/cr.2008.24. View

Cohen C, Zavala-Pompa A, Sequeira J, Shoji M, Sexton D, Cotsonis G . Mitogen-actived protein kinase activation is an early event in melanoma progression. Clin Cancer Res. 2002; 8(12):3728-33. View

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob S, Patel T . MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology. 2007; 133(2):647-58. PMC: 4285346. DOI: 10.1053/j.gastro.2007.05.022. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

10.

Chang T, Yu D, Lee Y, Wentzel E, Arking D, West K . Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 2007; 40(1):43-50. PMC: 2628762. DOI: 10.1038/ng.2007.30. View

11.

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

12.

Mendell J . miRiad roles for the miR-17-92 cluster in development and disease. Cell. 2008; 133(2):217-22. PMC: 2732113. DOI: 10.1016/j.cell.2008.04.001. View

13.

Maelandsmo G, Florenes V, Hovig E, Oyjord T, Engebraaten O, Holm R . Involvement of the pRb/p16/cdk4/cyclin D1 pathway in the tumorigenesis of sporadic malignant melanomas. Br J Cancer. 1996; 73(8):909-16. PMC: 2075830. DOI: 10.1038/bjc.1996.181. View

14.

Leivonen S, Makela R, Ostling P, Kohonen P, Haapa-Paananen S, Kleivi K . Protein lysate microarray analysis to identify microRNAs regulating estrogen receptor signaling in breast cancer cell lines. Oncogene. 2009; 28(44):3926-36. DOI: 10.1038/onc.2009.241. View

15.

Ryu B, Kim D, DeLuca A, Alani R . Comprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progression. PLoS One. 2007; 2(7):e594. PMC: 1895889. DOI: 10.1371/journal.pone.0000594. View

16.

Li X, Yan P, Shao Z . Downregulation of miR-193b contributes to enhance urokinase-type plasminogen activator (uPA) expression and tumor progression and invasion in human breast cancer. Oncogene. 2009; 28(44):3937-48. DOI: 10.1038/onc.2009.245. View

17.

Tang L, Tron V, Reed J, Mah K, Krajewska M, Li G . Expression of apoptosis regulators in cutaneous malignant melanoma. Clin Cancer Res. 1998; 4(8):1865-71. View

18.

Zhang X, Chen J, Radcliffe T, Lebrun D, Tron V, Feilotter H . An array-based analysis of microRNA expression comparing matched frozen and formalin-fixed paraffin-embedded human tissue samples. J Mol Diagn. 2008; 10(6):513-9. PMC: 2570634. DOI: 10.2353/jmoldx.2008.080077. View

19.

Pollock P, Harper U, Hansen K, Yudt L, Stark M, Robbins C . High frequency of BRAF mutations in nevi. Nat Genet. 2002; 33(1):19-20. DOI: 10.1038/ng1054. View

20.

Cummins D, Cummins J, Pantle H, Silverman M, Leonard A, Chanmugam A . Cutaneous malignant melanoma. Mayo Clin Proc. 2006; 81(4):500-7. DOI: 10.4065/81.4.500. View