MiR‑370 promotes apoptosis in colon cancer by directly targeting MDM4

Abstract

MicroRNA (miR)-370 functions as a tumor suppressor or promoter in several cancers. However, the expression and biological role of miR-370 in colon cancer remains undefined. In the present study, miR-370 expression in both normal and malignant colon tissues was quantified by quantitative polymerase chain reaction. An in vitro cell viability and apoptosis assay and an in vitro xenograft tumor model were employed to investigate the role of miR-370 on colon cancer growth. Furthermore, the potential direct target of miR-370 was identified using a luciferase assay. Our results demonstrate that down-regulation of miR-370 expression occurs in malignant tissues and miR-370 expression is inversely correlated with tumor grade. Moreover, we determined that miR-370 functions as a tumor suppressor in colon cancer by inhibiting cell proliferation and promoting cell apoptosis. In addition, overexpression of miR-370 impairs xenograft tumor growth in nude mice. Mechanistically, mouse double minute 4 (MDM4) was demonstrated to be a potential direct target of miR-370, inducing apoptosis in colon cancer. Collectively, these findings suggest that upregulation of miR-370 may impair colon tumor growth by directly targeting MDM4. These findings provide a new direction for the diagnosis and treatment of colon cancer.

<p>miR-370-3p Alleviates Ulcerative Colitis-Related Colorectal Cancer in Mice Through Inhibiting the Inflammatory Response and Epithelial-Mesenchymal Transition</p>

“…The previous study has demonstrated the role of miR-370 in inhibiting proliferation and inducing apoptosis in CRC cells. 25 Here, we focused on the effect of miR-370-3p on the proliferation and EMT of colon cancer cells. HCT116 and SW620 cells with the lowest expression of miR-370 25 were selected for this study.…”

“…25 Here, we focused on the effect of miR-370-3p on the proliferation and EMT of colon cancer cells. HCT116 and SW620 cells with the lowest expression of miR-370 25 were selected for this study. The regulatory effect of miR-370-3p on the proliferation of HCT116 cells and SW620 cells was evaluated by using CCK-8 assay.…”

“…As shown in Figure 5A, miR-370-3p significantly decreased the proliferation of these two cells compared with the corresponding controls, which was in line with the prior study. 25 The expression changes in epithelial and mesenchymal markers were determined by Western blot. miR-370-3p markedly elevated E-cadherin expression and reduced N-cadherin and Vimentin expression in HCT116 cells and SW620 cells ( Figure 5B), which indicated that miR-370-3p inhibited EMT of colon cancer cells.…”

“…Based on the interaction of miR-370-3p with β-catenin, we further explored whether miR-370-3p affected the progression of colon cancer through regulating β-catenin. According to the previous study, 25 HT29 cells with the highest expression of miR-370 were used for further experiments. The results of CCK-8 assay showed that inhibiting miR-370-3p led to a significant increase in the proliferation of colon cancer cells, while knockdown of β-catenin notably suppressed this effect ( Figure 7A).…”

Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer

“…In agreement, MDM4 gene has been detected in about 50% of CRC patients and plays an important negative regulator role of p53 [ 35 ]. In CRC patients, MDM4 is regulated by several factors [ 36 ] and represents a target of miR-370 [ 37 ]. Regarding THBD gene, it encodes for thrombomodulinand which is resulted hypermethylated in early-stage CRC [ 38 ].…”