Abstract
BackgroundGrowing evidence suggests that MiRNAs play essential roles in the initiation and progression of colorectal cancer (CRC). The aberrant expression of miR-384 has been reported in some cancers. However, the role and mechanism of miR-384 in CRC proliferation remains unknown.MethodsThe expression of miR-384 was detected in CRC and their paired normal tissues by real-time PCR. In vivo and in vitro assays were conducted to confirm the role of miR-384 in the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that AKT3 was the target gene of miR-384. Finally, Spearman’s correlation analyses was carried out to analyze the relationship between miR-384 expression and AKT3 expression in CRC.ResultsMiR-384 was down‑regulated in CRC tissues. The in vivo and vitro functional assays verified that the ectopic upregulation of miR-384 inhibited the proliferation of CRC and the inhibition of miR-384 promoted the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro functional assays confirmed AKT3 as the target gene of miR-384. The expression of miR-384 was negatively correlated with the expressions of AKT3.ConclusionOur study verified that miR-384 could significantly suppress the proliferation of CRC by directing targeting AKT3.
Highlights
Growing evidence suggests that MiRNAs play essential roles in the initiation and progression of colo‐ rectal cancer (CRC)
Student’s t test showed that the expression level of microRNA 384 (miR-384) in CRC tissues samples was significantly lower than that in adjacent normal tissues (Fig. 1b, c). These results showed that miR-384 was down-regulated in CRC tissues
Over‐expression of miR‐384 inhibited the proliferation of CRC cells in vitro and in vivo To explore the possible role of miR-384 on the proliferation of CRC, MTT, soft agar and colony formation assay were performed with the stable cells of SW480/miR-384, SW480/Vector, HCT116/miR-384 and HCT116/Vector (Fig. 2a)
Summary
Growing evidence suggests that MiRNAs play essential roles in the initiation and progression of colo‐ rectal cancer (CRC). The initiation of CRC is a complicated process which includes the activation of oncogenes, the inactivation of tumor suppressor genes and multiple risk factors [4, 5]. Numerous genetic alterations, such as the microsatellite instability, PIK3CA, RAS and BRAF mutations, have been recognized to be involved in the tumorigenesis of CRC [6, 7]. In-depth study of the molecular mechanism in the initiation and progression of CRC is significant for MicroRNAs (miRNAs) are small non-coding RNA molecules which are highly conserved in evolution and participate in the regulation of gene expression by directly being bound to the 3′-untranslated region (3′-UTR) of their target mRNAs [8, 9]. MicroRNA-338-3p is down-regulated in thyroid cancer tissues and inhibits the progression of thyroid cancer by repressing AKT3 expression [14]
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