Furthermore, we indicated that overexpression of HOXA11-AS decreased the miR-214-3p expression and the expression of miR-214-3p was negatively related with the HOXA11-AS expression in HCC samples.
Further, we validated Krüppel-like factor 5 (KLF5) as a direct target of miR-214-5p, and was upregulated in HCC and inversely correlated with the expression of miR-214-5p.
Correction to: MicroRNA-214-3p inhibits proliferation and cell cycle progression by targeting MELK in hepatocellular carcinoma and correlates cancer prognosis.
In the current study, miRNA expression profile screening was performed using SYBR Green-Based qRT-PCR array in TR-overexpressing HepG2 cells. miR-214-3p, which is expressed at low levels in HCC, was stimulated upon T<sub>3</sub> application.
Expressions of miR-214-3p in 98 HCC patients and three HCC cell lines were detected by quantitative reverse transcription PCR (qRT-PCR) to explore the association of miR-214-3p expression and clinicopathological characteristics.
The results demonstrated that the expression levels of human miR‑214 were reduced in HCC tissues and liver cancer cell lines compared with in control tissues and cells.
Network analysis revealed that several miRNAs such as miR-381-3p, miR-142a-3p, miR-214-3p and TFs such as Egr1, Atf3 and Klf4 were the core regulators in HCC.
On the contrary, high miR-214 expression significantly predicted favorable DFS/PFS/RFS (HR=0.50, 95%CI: 0.31-0.82, <i>P</i>=0.00) in hepatocellular carcinoma (HCC) group.
Furthermore, the inhibition effect of miR-214 on E2F2, cyclin-dependent kinase (CDK) 3 and CDK6 expression was assessed in HCC cell lines with miR-214 mimics/inhibitors to increase/decrease miR-214 expression.
In situ analysis revealed that UCP2 is a putative target of miR-214miR-214 expression is significantly down-regulated in HCC patient samples as compared with normal adjacent tissues and in cell line, human hepatoblastoma cells (HuH6), with high UCP2 protein expression.
In conclusion, our findings have shown that the SNP rs111904020 (U/G) in STAT3 3'UTR acted as promotion factors in the HCC development through disrupting the regulatory role of miR-214 in STAT3 expression.
MicroRNAs are short regulatory RNAs that are able to post-transcriptionally modulate gene expression and that have crucial roles in the control of physiological and pathological processes including cancer onset, growth, and progression. miR-214, located inside the sequence of the long noncoding Dmn3os transcript, contributes to the regulation of normal and cancer cell biology, even if it operates in a context-dependent and sometimes contradictory manner. miR-214 is deregulated in several human tumors including melanoma, breast, ovarian, gastric, and hepatocellular carcinomas. miR-214's pleiotropic and tumor-specific contribution to various cancer formation and progression hallmarks is achieved via its several target genes.
In conclusion, the featured miRNAs (the upregulated miRNA‑224 and downregulated miRNA‑214) and their target genes are significant in the occurrence and development of HCC, which is likely to be significant for the identification of therapeutic targets and biomarkers to aid in the treatment of HCC.
In comparison with GSD Ia HCA, the upregulation of miR-130b and downregulation of miR-199a-5p, miR-199b-5p, and miR-214 were more significant in HCC cell lines.
Further qRT-PCR analysis of 50 HCC tissues from an independent cohort of HCC patients of whom 29 with early recurrent disease (<2 years) and 21 with late recurrent disease demonstrated that the suppression of miR-214 was significantly more suppressed in samples from HCC patients with early recurrent disease compared those from patients with no recurrence.
These findings indicate that miR-214 serves as tumor suppressor and plays substantial roles in inhibiting the tumorigenesis of HCC through suppression of β-catenin.