IGF2-derived MiR-483 Mediated Oncofunction by Suppressing DLC-1 and Associated with Colorectal Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jul 2

PMID 27366946

Citations 17

Authors

Hengmi Cui

Yuan Liu

Jingrui Jiang

YangYang Liu

Zhe Yang

Shaogen Wu

Wangsen Cao

Isabelle H Cui

Chenggong Yu

Affiliations

Soon will be listed here.

Abstract

Emerging evidence indicates that IGF2 plays an important role in various human malignancies, including colorectal cancer (CRC). Hsa-miR-483 is located within intron 7 of the IGF2 locus. However, the mechanism by which increased IGF2 induces carcinogenesis remains largely elusive. DLC-1 has been identified as a candidate tumor suppressor. In this study, we aimed at investigating whether miR-483 transcription is IGF2-dependent, identifying the functional target of miR-483, and evaluating whether tissue and serum miR-483-3p or miR-483-5p levels are associated with CRC. Our results showed that sequences upstream miR-483 had undetectable promoter activity and levels of IGF2, miR-483-3p, and miR-483-5p were synchronously increased in CRC tissues. Positive correlations between IGF2 and miR-483-3p (r=0.4984, ***p<0.0001), and between IGF2 and miR-483-5p (r=0.6659, ***p<0.0001) expression were found. In addition, patients with CRC had a significantly higher serum miR-483-5p level (*p<0.05) compared to normal controls. DLC-1 expression was decreased in colorectal cancer tissues and diminished through transient transfection with miR-483-3p. Our results suggest that IGF2 may exert its oncofunction, at least partly, through its parasitic miR-483 which suppressed DLC-1 in CRC cells. Thus, miR-483 might serve as a new target for therapy and a potential biomarker for the detection of colorectal cancer.

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References

Cruz-Correa M, Cui H, Giardiello F, Powe N, Hylind L, Robinson A . Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology. 2004; 126(4):964-70. DOI: 10.1053/j.gastro.2003.12.051. View

Du X, Qian X, Papageorge A, Schetter A, Vass W, Liu X . Functional interaction of tumor suppressor DLC1 and caveolin-1 in cancer cells. Cancer Res. 2012; 72(17):4405-16. PMC: 6264793. DOI: 10.1158/0008-5472.CAN-12-0777. View

Durkin M, Yuan B, Zhou X, Zimonjic D, Lowy D, Thorgeirsson S . DLC-1:a Rho GTPase-activating protein and tumour suppressor. J Cell Mol Med. 2007; 11(5):1185-207. PMC: 4401278. DOI: 10.1111/j.1582-4934.2007.00098.x. View

Rayner K, Suarez Y, Davalos A, Parathath S, Fitzgerald M, Tamehiro N . MiR-33 contributes to the regulation of cholesterol homeostasis. Science. 2010; 328(5985):1570-3. PMC: 3114628. DOI: 10.1126/science.1189862. View

Michael M, O Connor S, van Holst Pellekaan N, Young G, James R . Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003; 1(12):882-91. View

Veronese A, Lupini L, Consiglio J, Visone R, Ferracin M, Fornari F . Oncogenic role of miR-483-3p at the IGF2/483 locus. Cancer Res. 2010; 70(8):3140-9. PMC: 4303586. DOI: 10.1158/0008-5472.CAN-09-4456. View

Abue M, Yokoyama M, Shibuya R, Tamai K, Yamaguchi K, Sato I . Circulating miR-483-3p and miR-21 is highly expressed in plasma of pancreatic cancer. Int J Oncol. 2014; 46(2):539-47. PMC: 4277249. DOI: 10.3892/ijo.2014.2743. View

Vu T, Nguyen A, Hoffman A . Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet. 2009; 19(5):901-19. PMC: 2816615. DOI: 10.1093/hmg/ddp558. View

Liao Y, Lo S . Deleted in liver cancer-1 (DLC-1): a tumor suppressor not just for liver. Int J Biochem Cell Biol. 2007; 40(5):843-7. PMC: 2323245. DOI: 10.1016/j.biocel.2007.04.008. View

10.

Orkin S, Goldman D, Sallan S . Development of homozygosity for chromosome 11p markers in Wilms' tumour. Nature. 1984; 309(5964):172-4. DOI: 10.1038/309172a0. View

11.

Miller S, Steele S . Novel molecular screening approaches in colorectal cancer. J Surg Oncol. 2012; 105(5):459-67. DOI: 10.1002/jso.21704. View

12.

Ma N, Wang X, Qiao Y, Li F, Hui Y, Zou C . Coexpression of an intronic microRNA and its host gene reveals a potential role for miR-483-5p as an IGF2 partner. Mol Cell Endocrinol. 2010; 333(1):96-101. DOI: 10.1016/j.mce.2010.11.027. View

13.

Reeve A, Housiaux P, Gardner R, Chewings W, Grindley R, Millow L . Loss of a Harvey ras allele in sporadic Wilms' tumour. Nature. 1984; 309(5964):174-6. DOI: 10.1038/309174a0. View

14.

Qu X, Zhao M, Wu S, Yu W, Xu J, Xu J . Circulating microRNA 483-5p as a novel biomarker for diagnosis survival prediction in multiple myeloma. Med Oncol. 2014; 31(10):219. DOI: 10.1007/s12032-014-0219-x. View

15.

Ng E, Chong W, Jin H, Lam E, Shin V, Yu J . Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut. 2009; 58(10):1375-81. DOI: 10.1136/gut.2008.167817. View

16.

Kaneda A, Feinberg A . Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. Cancer Res. 2005; 65(24):11236-40. DOI: 10.1158/0008-5472.CAN-05-2959. View

17.

Najafi-Shoushtari S, Kristo F, Li Y, Shioda T, Cohen D, Gerszten R . MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010; 328(5985):1566-9. PMC: 3840500. DOI: 10.1126/science.1189123. View

18.

Koufos A, Hansen M, Lampkin B, Workman M, Copeland N, Jenkins N . Loss of alleles at loci on human chromosome 11 during genesis of Wilms' tumour. Nature. 1984; 309(5964):170-2. DOI: 10.1038/309170a0. View

19.

Chen Y, Boyartchuk V, Lewis B . Differential roles of insulin-like growth factor receptor- and insulin receptor-mediated signaling in the phenotypes of hepatocellular carcinoma cells. Neoplasia. 2009; 11(9):835-45. PMC: 2735682. DOI: 10.1593/neo.09476. View

20.

Randhawa G, Cui H, Barletta J, Talpaz M, Kantarjian H, Deisseroth A . Loss of imprinting in disease progression in chronic myelogenous leukemia. Blood. 1998; 91(9):3144-7. View