IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer

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.

Overexpression of miR‐301a‐3p promotes colorectal cancer cell proliferation and metastasis by targeting deleted in liver cancer‐1 and runt‐related transcription factor 3

“…22 In addition, DLC-1 induced apoptosis and inhibited the growth and invasion of colon cancer cells. 24,25 In this study, it suggested that DLC-1 was regulated by miR-301a-3p, and overexpression of DLC-1 could inhibit proliferation, invasion, and migration. 24,25 In this study, it suggested that DLC-1 was regulated by miR-301a-3p, and overexpression of DLC-1 could inhibit proliferation, invasion, and migration.…”

Infantile hemangioma: factors causing recurrence after propranolol treatment

“…A recent study also reported that the let-7 family of miRNAs was potential biomarkers for grade prediction in breast cancer (34). MiR-483 has an important role in suppressing the deleted in liver cancer-1 (DLC-1) gene and may thus serve as a new therapeutic target and a potential biomarker of colorectal cancer (35), and miR-494 has been demonstrated to inhibit ovarian cancer cell proliferation and promote apoptosis by targeting fibroblast growth factor receptor 2 (ref. 36).…”

Plasma miRNA‐based signatures in CRC screening programs

“…miR‐483‐5p is expressed in multiple cancers and has been proposed as a circulating biomarker of tumor presence . In CRC it can suppress the DLC‐1 gene (deleted in liver cancer 1), inducing cell proliferation . Altered expression of miR‐186 affects tumor growth, invasion and metastasis in various cancers .…”

“…41 In CRC it can suppress the DLC-1 gene (deleted in liver cancer 1), inducing cell proliferation. 42 Altered expression of miR-186 affects tumor growth, invasion and metastasis in various cancers. 43 For this miRNA, there were significant differences in expression between plasma from patients with polyps or adenomas and controls without lesions recruited from the Bowel Cancer Screening Program in the United Kingdom.…”