MiR-191 Promotes Tumorigenesis of Human Colorectal Cancer Through Targeting C/EBPβ

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Mar 19

PMID 25784653

Citations 38

Authors

Xiao-Fei Zhang

Ke-Ke Li

Lu Gao

Shang-Ze Li

Ke Chen

Jun-Bin Zhang

Di Wang

Rong-Fu Tu

Jin-Xiang Zhang

Kai-Xiong Tao

Guobin Wang

Xiao-Dong Zhang

Affiliations

Soon will be listed here.

Abstract

MicroRNA-191 (miR-191), a small non-coding RNA, is involved in disease development and cancer diagnosis and prognosis. However, how miR-191 functions in colorectal cancer remains largely unclear. In this study, we show that miR-191 is highly expressed in colon tumor tissues, and that inhibition of miR-191 leads to decreased cell growth, proliferation and tumorigenicity in a xenograft model. Overexpression of miR-191 in colorectal cancer cell lines alters cell cycle progression and cell resistance to 5-Fu induced cell apoptosis. Mechanistic studies demonstrated that miR-191 directly binds to the 3'UTR of the C/EBPβ mRNA and mediates a decrease in the mRNA and protein expression of C/EBPβ. We further showed that C/EBPβ induces growth arrest in a colorectal cancer cell line and that its expression is negatively correlated with the miR-191 level in patient samples. Our findings suggest that miR-191 may be a potential gene therapy target for the treatment of colorectal cancer.

Citing Articles

Germline variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase ().

Zhang T, Ambrodji A, Huang H, Bouchonville K, Etheridge A, Schmidt R Elife. 2024; 13.

PMID: 38686795 PMC: 11060711. DOI: 10.7554/eLife.94075.

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.

Elmahboub Y, Albash R, Magdy William M, Rayan A, Hamed N, Ousman M Molecules. 2024; 29(7).

PMID: 38611893 PMC: 11013883. DOI: 10.3390/molecules29071614.

Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.

Ni J, Xi X, Xiao S, Xiao X Mol Biotechnol. 2024; 66(5):1314-1325.

PMID: 38270757 DOI: 10.1007/s12033-023-01034-0.

Germline variant determines epigenetic regulation of the anti-cancer drug metabolism gene dihydropyrimidine dehydrogenase ().

Zhang T, Ambrodji A, Huang H, Bouchonville K, Etheridge A, Schmidt R bioRxiv. 2023; .

PMID: 37961517 PMC: 10635067. DOI: 10.1101/2023.11.01.565230.

MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway.

Wang Z, Guan W, Ma Y, Zhou X, Song G, Wei J BMC Cancer. 2023; 23(1):668.

PMID: 37460940 PMC: 10351167. DOI: 10.1186/s12885-023-11113-9.

References

Garzon R, Volinia S, Liu C, Fernandez-Cymering C, Palumbo T, Pichiorri F . MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood. 2008; 111(6):3183-9. PMC: 2265455. DOI: 10.1182/blood-2007-07-098749. View

Nerlov C . Transcriptional and translational control of C/EBPs: the case for "deep" genetics to understand physiological function. Bioessays. 2010; 32(8):680-6. DOI: 10.1002/bies.201000004. View

Xi Y, Formentini A, Chien M, Weir D, Russo J, Ju J . Prognostic Values of microRNAs in Colorectal Cancer. Biomark Insights. 2007; 2:113-121. PMC: 2134920. View

Lee Y, Dutta A . The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007; 21(9):1025-30. PMC: 1855228. DOI: 10.1101/gad.1540407. View

Pal P, Lochab S, Kanaujiya J, Sanyal S, Trivedi A . Ectopic expression of hC/EBPs in breast tumor cells induces apoptosis. Mol Cell Biochem. 2009; 337(1-2):111-8. DOI: 10.1007/s11010-009-0290-3. View

Akira S, Isshiki H, Sugita T, TANABE O, Kinoshita S, Nishio Y . A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990; 9(6):1897-906. PMC: 551896. DOI: 10.1002/j.1460-2075.1990.tb08316.x. View

Zhou J, Zhou Y, Yin B, Hao W, Zhao L, Ju W . 5-Fluorouracil and oxaliplatin modify the expression profiles of microRNAs in human colon cancer cells in vitro. Oncol Rep. 2009; 23(1):121-8. View

Umek R, Friedman A, McKnight S . CCAAT-enhancer binding protein: a component of a differentiation switch. Science. 1991; 251(4991):288-92. DOI: 10.1126/science.1987644. View

Wessells J, Yakar S, Johnson P . Critical prosurvival roles for C/EBP beta and insulin-like growth factor I in macrophage tumor cells. Mol Cell Biol. 2004; 24(8):3238-50. PMC: 381667. DOI: 10.1128/MCB.24.8.3238-3250.2004. View

10.

Grimm S, Rosen J . The role of C/EBPbeta in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 2003; 8(2):191-204. DOI: 10.1023/a:1025900908026. View

11.

Besson A, Dowdy S, Roberts J . CDK inhibitors: cell cycle regulators and beyond. Dev Cell. 2008; 14(2):159-69. DOI: 10.1016/j.devcel.2008.01.013. View

12.

He L, Thomson J, Hemann M, Hernando-Monge E, Mu D, Goodson S . A microRNA polycistron as a potential human oncogene. Nature. 2005; 435(7043):828-33. PMC: 4599349. DOI: 10.1038/nature03552. View

13.

Cummins J, He Y, Leary R, Pagliarini R, Diaz Jr L, Sjoblom T . The colorectal microRNAome. Proc Natl Acad Sci U S A. 2006; 103(10):3687-92. PMC: 1450142. DOI: 10.1073/pnas.0511155103. View

14.

Fang L, Li H, Wang L, Hu J, Jin T, Wang J . MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget. 2014; 5(10):2974-87. PMC: 4102784. DOI: 10.18632/oncotarget.1614. View

15.

Hara T, Jones M, Subramanian M, Li X, Ou O, Zhu Y . Selective targeting of KRAS-mutant cells by miR-126 through repression of multiple genes essential for the survival of KRAS-mutant cells. Oncotarget. 2014; 5(17):7635-50. PMC: 4202150. DOI: 10.18632/oncotarget.2284. View

16.

Shimizu Y, Kishimoto T, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H . CCAAT/enhancer binding protein-beta promotes the survival of intravascular rat pancreatic tumor cells via antiapoptotic effects. Cancer Sci. 2007; 98(11):1706-13. PMC: 11159374. DOI: 10.1111/j.1349-7006.2007.00596.x. View

17.

Ebert M, Neilson J, Sharp P . MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007; 4(9):721-6. PMC: 3857099. DOI: 10.1038/nmeth1079. View

18.

Sun L, Fu B, Liu D . Systemic delivery of full-length C/EBP beta/liposome complex suppresses growth of human colon cancer in nude mice. Cell Res. 2005; 15(10):770-6. DOI: 10.1038/sj.cr.7290346. View

19.

Volinia S, Calin G, Liu C, Ambs S, Cimmino A, Petrocca F . A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006; 103(7):2257-61. PMC: 1413718. DOI: 10.1073/pnas.0510565103. View

20.

Hirata M, Kugimiya F, Fukai A, Ohba S, Kawamura N, Ogasawara T . C/EBPbeta Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57. PLoS One. 2009; 4(2):e4543. PMC: 2638010. DOI: 10.1371/journal.pone.0004543. View