Back to Search
Start Over
Regulation of antitumor miR‐144‐5p targets oncogenes: Direct regulation of syndecan‐3 and its clinical significance
- Source :
- Cancer Science
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
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 × 10-5 ). 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.
- Subjects :
- Male
0301 basic medicine
renal cell carcinoma
Cancer Research
Syndecan 1
Pathogenesis
03 medical and health sciences
SDC3
0302 clinical medicine
Cell Movement
Cell Line, Tumor
microRNA
Humans
Neoplasm Invasiveness
RNA, Small Interfering
Genetics, Genomics, and Proteomics
Carcinoma, Renal Cell
Gene
antitumor
Aged
Cell Proliferation
biology
TRIP13
CENPF
Original Articles
Oncogenes
General Medicine
Middle Aged
Prognosis
Kidney Neoplasms
MicroRNAs
030104 developmental biology
Oncology
miR‐144‐5p
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Cancer research
Syndecan-3
Original Article
Female
RNA Interference
TMC8
Subjects
Details
- ISSN :
- 13497006 and 13479032
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Cancer Science
- Accession number :
- edsair.doi.dedup.....b6a08909d149eeacbdf0b6ba4a1b0083