MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer.
PURPOSE
The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified.


EXPERIMENTAL DESIGN
We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion.


RESULTS
Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489 expression than those with lower miR-489 expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7.


CONCLUSIONS
We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
['Gao|S|S|http://orcid.org/0000-0002-7681-8226', 'Liu|H|H|', 'Hou|S|S|', 'Wu|L|L|', 'Yang|Z|Z|', 'Shen|J|J|', 'Zhou|L|L|', 'Zheng|S-S|SS|', 'Jiang|B|B|']
D000818:Animals D017209:Apoptosis D014408:Biomarkers, Tumor D002465:Cell Movement D049109:Cell Proliferation D015179:Colorectal Neoplasms D018450:Disease Progression D005260:Female D015972:Gene Expression Regulation, Neoplastic D006655:Histone Deacetylases D006801:Humans D008113:Liver Neoplasms D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D008875:Middle Aged D009361:Neoplasm Invasiveness D009364:Neoplasm Recurrence, Local D011379:Prognosis D015996:Survival Rate D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
miR-489 HDAC7 Colorectal cancer Tumor invasion