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Regulation of antitumor miR-144-5p targets oncogenes: Direct regulation of syndecan-3 and its clinical significance.
- Source :
-
Cancer science [Cancer Sci] 2018 Sep; Vol. 109 (9), pp. 2919-2936. Date of Electronic Publication: 2018 Jul 28. - Publication Year :
- 2018
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Abstract
- In the human genome, miR-451a, miR-144-5p (passenger strand), and miR-144-3p (guide strand) reside in clustered microRNA (miRNA) sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR-451a: P = .00305; miR-144-5p: P = .00128; miR-144-3p: P = 9.45 × 10 <superscript>-5</superscript> ). We previously reported that miR-451a acted as an antitumor miRNA in RCC cells. Involvement of the passenger strand of the miR-144 duplex in the pathogenesis of RCC is not well understood. Functional assays showed that miR-144-5p and miR-144-3p significantly reduced cancer cell migration and invasive abilities, suggesting these miRNAs acted as antitumor miRNAs in RCC cells. Analyses of miR-144-5p targets identified a total of 65 putative oncogenic targets in RCC cells. Among them, high expression levels of 9 genes (FAM64A, F2, TRIP13, ANKRD36, CENPF, NCAPG, CLEC2D, SDC3, and SEMA4B) were significantly associated with poor prognosis (P < .001). Among these targets, expression of SDC3 was directly controlled by miR-144-5p, and its expression enhanced cancer cell aggressiveness. We identified genes downstream by SDC3 regulation. Data showed that expression of 10 of the downstream genes (IL18RAP, SDC3, SH2D1A, GZMH, KIF21B, TMC8, GAB3, HLA-DPB2, PLEK, and C1QB) significantly predicted poor prognosis of the patients (P = .0064). These data indicated that the antitumor miR-144-5p/oncogenic SDC3 axis was deeply involved in RCC pathogenesis. Clustered miRNAs (miR-451a, miR-144-5p, and miR-144-3p) acted as antitumor miRNAs, and their targets were intimately involved in RCC pathogenesis.<br /> (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Aged
Carcinoma, Renal Cell genetics
Carcinoma, Renal Cell mortality
Cell Line, Tumor
Cell Proliferation genetics
Female
Humans
Kidney Neoplasms genetics
Kidney Neoplasms mortality
Male
Middle Aged
Neoplasm Invasiveness genetics
Prognosis
RNA Interference
RNA, Small Interfering genetics
Syndecan-3 metabolism
Carcinoma, Renal Cell pathology
Cell Movement genetics
Kidney Neoplasms pathology
MicroRNAs genetics
Oncogenes genetics
Syndecan-3 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 109
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 29968393
- Full Text :
- https://doi.org/10.1111/cas.13722