miR‑451 suppresses the malignant characteristics of colorectal cancer via targeting SAMD4B

Abstract

Cancer metastasis and recurrence are major causes of poor survival in patients with colorectal cancer (CRC). Therefore, the biological behavior of microRNA (miR)-451 in CRC deserves further investigation. Reverse transcription-quantitative PCR was applied to measure the relative expression of miR-451 in blood serum specimens from patients with CRC and CRC cells. In vitro , HCT116 cells were transfected with miR-451 mimics, a miR-451 inhibitor, or SAMD4B plasmids. Proliferation, migration and apoptosis were measured using CCK-8, Transwell assays and flow cytometry, respectively. Luciferase reporter assay was used to identify targets of miR-451 and western blotting performed to explore the internal mechanisms of miR-451 regulation. In vivo , the effect of miR-451 and SAMD4B plasmids on tumor growth was analyzed using a nude mouse xenograft model. Results indicated that serum miR-451 expression was lower in patients with CRC compared with healthy controls. Patients with elevated expression of miR-451 had longer survival times compared with those with low expression. Overexpression of miR-451 inhibited proliferation and migration, promoted apoptosis and enhanced the sensitivity of CRC cells to chemotherapy. SAMD4B was identified as a direct target of miR-451 using miRNA target prediction programs and dual luciferase reporter assay validated the binding site of miR-451 in the 3-′UTR region of SAMD4B. Further studies confirmed that miR-451 inhibited CRC progression via targeting SAMD4B. Results indicated that miR-451 is essential for blocking tumor growth via targeting SAMD4B in vivo and in vitro . The miR-451/SAMD4B axis may serve as a novel therapeutic target in patients with CRC.

Identification of Differentially Expressed Genes and microRNAs in the Gray and White Feather Follicles of Shitou Geese

“…Currently, there is limited direct evidence linking these specific miRNAs to feather coloration. miR-451 has been studied in the context of its involvement in cancers [74][75][76], indicating its diverse functions beyond pigmentation. Dre-miR-2188, on the other hand, has been implicated in targeting Nrp2a and regulating proper intersegmental vessel development in zebrafish embryos [77], suggesting a role in embryonic vascular development.…”

RNA binding protein SAMD4: current knowledge and future perspectives

“…Colorectal cancer occurrence is mainly caused by the genetic and epigenetic changes of colon epithelial cells, as well as the activation of oncogenes and the inactivation of tumor suppressor genes [ 70 , 71 ]. The latest research work demonstrates that miR‑451 suppresses the malignant characteristics of colorectal cancer cells through targeting SAMD4B [ 72 ]. MicroRNAs (miRNAs) are a class of regulatory RNAs composed of about 22 nucleotides, which can mediate post-transcriptional inhibition by binding to the 3’-UTR of the targeted mRNA, and thereby regulating gene expression [ 73 ].…”

“…Dual luciferase reporter assay validated that miR-451 could specifically bind to the 3’-UTR of SAMD4B mRNA to down-regulate the expression of SAMD4B, thus inhibiting proliferation and promoting apoptosis of colorectal cancer cells. Conversely, overexpression of SAMD4B attenuated miR-451-induced apoptosis and promoted colorectal cancer progression [ 72 ]. This study suggests that miR-451/SAMD4B axis may serve as a new therapeutic target for the treatment of patients with colorectal cancer.…”

“…In addition, transcriptomic analysis investigates that Polygonatum sibiricum polysaccharide (PSP) treatment can regulate the expression level of SAMD4 mRNA [ 14 ]. More interestingly, miR-451 can downregulate the expression of SAMD4B both at mRNA and protein levels [ 72 ].…”

Long noncoding RNA THOR, a novel target biomolecule, is involved in the progression of colorectal cancer

“…According to GLOBOCAN (Global Cancer Observatory) data, there were nearly 2 million new cases of colorectal cancer and nearly 1 million-related deaths in 2020, making it the second most common cause of cancer-related death [2,3]. The pathogenesis of colorectal cancer is complex; it involves the regulation of genetics, epigenetics, the tumor microenvironment and other factors [4,5]. Although many molecules have been reported to promote or inhibit colorectal cancer progression, the specific mechanisms underlying the occurrence and development of colorectal cancer have not yet been fully elucidated [6,7].…”