MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the main cause of cancer-related deaths. It’s reported that bone marrow mesenchymal stem cells (BMSCs) affects tumor development through secreting exosomes. This study aims to investigate the function of BMSCs-derived exosome miR-4461 in CRC. The results of qRT-PCR showed that miR-4461 expression in DLD1, HCT116 and SW480 CRC cells and CRC tissues was lower than that in FHC cells and normal tissues, respectively. And COPB2 mRNA expression was negatively correlated with miR-4461. Western blot was used to detect COPB2 protein expression. Dual-luciferase reporter assay results revealed that miR-4461 targeted COPB2. Transwell assay and CCK-8 assay demonstrated that COPB2 knockdown inhibited HCT116 and SW480 cells proliferation, migration and invasion abilities. Furthermore, BMSCs-derived exosome miR-4461 downregulated COPB2 expression and inhibited HCT116 and SW480 cells migration and invasion. The findings demonstrated that miR-4461 could be a potential target for the diagnosis and treatment of colorectal cancer.

miR-4461 Regulates the Proliferation and Metastasis of Ovarian Cancer Cells and Cisplatin Resistance

“…Increasing evidence demonstrated that miRNAs are important regulators in ovarian cancer, however, few miRNAs have been used clinically. Earlier studies pointed out that miR-4461 was a tumor suppressor in renal cell carcinoma and colorectal cancer (13,14). We found that interference of miR-4461 expression in OC cells suppressed cell proliferation and metastasis.…”

“…The conclusion that miR-4461 suppresses tumorigenesis of renal cell carcinoma is given in the previous research (13). Moreover, the miR-4461 which originated from the bone marrow mesenchymal stem cell exosomes suppresses tumorigenesis by reducing COPB2 expression in colorectal cancer (14). Whereas, the function of miR-4461 in OC was unclear.…”

Proteomic and transcriptomic studies of BGC823 cells stimulated with Helicobacter pylori isolates from gastric MALT lymphoma

“…For example, our results showed miR4461 and miR3064 were down-regulated in BGC823 cell line infected by GML isolates compared with 26695 ( S6 and S7 Tables). It has been shown that miR4461 were involved in the tumorigenesis of colorectal cancer [ 42 ] and miR3064 can inhibit cell proliferation and invasion in ovarian cancer [ 43 ]. We also found IL-10, IL-17RD, IL-1A, IL-21R, IL-1B, TNFAIP8L1, TNFSF9, TNFSF14, TNFSF15, CCL28, CCL22 and CCL20 were down-regulated ( S6 and S7 Tables).…”

Human Bone Marrow-Derived Mesenchymal Stem Cell-Secreted Exosomes Overexpressing Microrna-124-3p Inhibit DLBCL Progression By Downregulating  NFATc1

“…In recent years, MSC-derived exosomes transfected with miRNAs have been shown to play essential roles in tumorigenesis and can serve as mediators in human cancers. Several studies have reported that exosomes released from bone marrow mesenchymal stem cells (MSCs) can carry microRNAs (miRNAs), which are involved in cancer cell proliferation, differentiation, and apoptosis [26][27][28]. However, the effect of human BMSC (hBMSC)-derived exosomes on the occurrence and progression of DLBCL remains poorly understood.…”