MiR-125b Suppression Inhibits Apoptosis and Negatively Regulates Sema4D in Avian Leukosis Virus-Transformed Cells

Abstract

Subgroup J avian leukosis virus (ALV-J), an oncogenic retrovirus, causes hemangiomas and myeloid tumors in chickens. We previously showed that miR-125b is down-regulated in ALV-J-induced tumors. This study aimed to investigate the possible role of miR-125b in ALV-J-mediated infection and tumorigenesis. Knockdown of miR-125b expression in HP45 cells reduced, whereas over-expression induced late-stage apoptosis. Bioinformatics analysis and luciferase activity assays indicate that miR-125b targets Semaphorin 4D/CD100 (Sema4D) by binding the 3′-untranslated region of messenger RNA (mRNA). Up-regulation of miR-125b in the DF1 cell line suppressed Sema4D expression, whereas miR-125 down-regulation increased Sema4D expression levels. To uncover the function of Sema4D during ALV-J infection, animal infection experiments and in vitro assays were performed and show that Sema4D mRNA levels were up-regulated in ALV-J-infected tissues and cells. Finally, functional experiments show that miR-125 down-regulation and Sema4D over-expression inhibited apoptosis in HP45 cells. These results suggest that miR-125b and its target Sema4D might play an important role in the aggressive growth of HP45 cells induced by avian leukosis viruses (ALVs). These findings improve our understanding of the underlying mechanism of ALV-J infection and tumorigenesis.

SEMA4D Knockdown Attenuates β‐Catenin‐Dependent Tumor Progression in Colorectal Cancer

“…In line with our findings, it has been indicated that SEMA4D silencing elevated the apoptosis rate of KYSE-150 and TE-10 cells [49]. In addition, the upregulation of SEMA4D in HP45 cells could suppress the apoptosis, and SEMA4D targeting by miR-125b could negatively regulate it and augment the apoptosis rate in avian leucosis virus-transformed cells [54]. As reported by Liu et al, it has been revealed that targeting of SEMA4D by miR-214 could prevent cell proliferation and induce apoptosis in ovarian cancer cells [55].…”

Transcriptome-wide N6-methyladenosine modification and microRNA jointly regulate the infection of avian leukosis virus subgroup J in vitro

“…The pathways of autophagy or mitophagy are also active research fields for viral infection and have been documented for ALV-J, which are mainly related to the virus–host interactions between viral replication and pathogenesis ( Liao et al, 2020 ; Xie et al, 2023 ). Meanwhile, the enriched MAPK, TNF, and Hippo signaling pathways have been discussed in the oncogenic mechanisms related to ALV-J ( Li et al, 2014 ; Dai M et al, 2016 ; Ren et al, 2019 ). Some of these reports have focused on aberrantly regulated miRNAs and their targets, and miRNAs in the cancer pathway were enriched according to the KEGG analysis for both DMGs and DEGs.…”

“…The related mechanisms mainly comprise promoter activation, enhancer activation, and nontermination transcription activation, which are related to the expression of proto-oncogenes driven by cis-acting elements in LTRs ( Fan and Johnson, 2011 ). In addition, insertional mutagenesis and activated/inactivated signaling pathways induced by ALV-J infection also dysregulated the transcription of microRNAs ( miRNAs ) ( Yao et al, 2015 ; Feng et al, 2017 ; Ren et al, 2019 ). mRNAs transfer genetic information from DNA to protein, and miRNAs act as epigenetic regulators of gene transcription ( Erson-Bensan and Begik, 2017 ).…”

MIR4435-2HG, miR-125b-5p, and Sema4D axis affects the aggressiveness of colorectal cancer cells

“…To characterize the action mechanism of Sema4D exacerbating CRC development, functional experiments were conducted and confirmed the binding of miR-125b-5p to Sema4D concurrent with the negative regulation of Sema4D by miR-125b-5p. Ren and colleagues have documented that miR-125b suppressed the tumor aggressiveness induced by subgroup J avian leukosis virus and enhanced apoptosis in chicken by binding to Sema4D [32]. miR-125b-5p was expressed at a low level in CRC tissues and cells, and upregulation of its expression exhibited significant inhibitory effects on CRC cell propagation and aggressiveness.…”