<p>MicroRNA-421 Inhibits Apoptosis by Downregulating Caspase-3 in Human Colorectal Cancer</p>

Abstract

Dysregulated microRNAs (miRNAs/miRs) have been reported to play significant roles in pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated that miR-421 regulates apoptosis in some cancers. Caspase-3 plays a key role in apoptosis, but the relationship between miR-421 and caspase-3 in CRC has not been determined. In this study, we investigated the role of miR-421 in CRC and the relationship between miR-421 and caspase-3. Methods: Expression of miR-421 and caspase-3 were detected in human paired CRC cancer tissues and corresponding paracancerous tissues. In situ detection of tissue, apoptosis was performed via the TUNEL assay. HCT116 and SW480 cell lines were subjected to several in vitro experiments to explore the relationship between miRNA421 and caspase-3 during apoptosis using miR421 mimics/antagomir and luciferase reporter assay. Apoptosis was measured by determining the levels and activity of caspase-3 as well as DNA fragmentation. Luciferase reporter assay was performed to determine the potential interaction of miR-421 with caspase-3. Results: The results showed that the expression of miR-421 in cancer tissues was higher than that in corresponding paracancerous tissues. Inhibition of miR-421 induced apoptosis, as shown by the upregulation of caspase-3 activity and expression as well as DNA fragmentation, which were attenuated by miR-421 mimic. We further showed that miR-421 targeted and inhibited CASP3 expression by targeting sites located in the 3ʹ-untranslated region (3ʹ-UTR) of CASP3 mRNA. Conclusion: This study demonstrated an anti-apoptotic role of miR-421 in CRC and identified caspase-3 gene as a direct target of miR-421. These findings provide a potential treatment strategy using miR-421 as a therapeutic target for CRC.

circ_0000567/miR-421/TMEM100 Axis Promotes the Migration and Invasion of Lung Adenocarcinoma and Is Associated with Prognosis

“…miR-224, miR-147b, and miR-31 are related to lymph node metastasis and prognosis in LUAD [46]. Recently, miR-421 was found to be dysregulated in breast and colon tumors [47,48].It has been reported that miR-421 promotes the development of osteosarcoma by regulating the target gene MCPIP1 and that it might serve as a valuable biomarker in patients with esophageal adenocarcinoma and osteosarcoma [49][50][51]. Chen et al found that overexpression of plasma miR-421 can act as a novel biomarker for the detection of precancerous lesions and early gastric cancer [52].…”

Aberrant Post-Transcriptional Regulation of Protein Expression in the Development of Chronic Obstructive Pulmonary Disease

“…In addition to miRNA playing fundamental roles in inflammation, many miRNAs are also implicated in regulating cell survival. Both miR-23a and miR-421, for example, repress caspase-9 and caspase-3, respectively [ 216 , 217 ]. miR-421 is downregulated in response to smoke [ 191 ], whereas the activity of caspase-3 is increased by smoke exposure [ 218 ].…”

Constructing Novel ceRNA Networks on MiR-616-3p Reveals LncRNAs as Potential Colorectal Cancer Prognostic Biomarkers

“…(Bian et al 2018) microRNAs (miRNAs) are a class of single-stranded, short, and conserved ncRNAs 18 ± 24 nucleotides in length that negatively modulate gene expression at the post-transcriptional level by binding to the 3untranslated region (3 UTR) of target genes. (Zhou et al 2020) Several studies have suggested that miRNAs regulate many physiological processes in the cell, including migration, invasion, cell proliferation, and apoptosis. Aberrant miRNAs also participate in the initiation, promotion, angiogenesis, metastasis, and drug resistance of several types of cancers.…”