EIF4A3-induced hsa_circ_0078136 inhibits the tumorigenesis of retinoblastoma via IL-17 signaling pathway.

Retinoblastoma (RB) is one of the most common intraocular cancers, with the highest prevalence among infants and young children under the age five. Numerous findings across the literature illustrate the involvement and significance of circular RNAs (circRNAs) in human malignancies, including RB. The current investigation attempted to decipher the exact roles and underlying mechanisms of a novel circRNA, hsa_circ_0078136, in RB progression. The hsa_circ_0078136 expression was evaluated in RB tumors and cell lines via qRT-PCR. The significance of hsa_circ_0078136 in RB was examined by performing CCK8 assay, transwell assays, western blotting of apoptotic and IL-17 signaling ligand molecules, and a subcutaneous xenograft tumor model. In addition, the interaction of circRNA and eukaryotic translation initiation factor 4A3 (EIF4A3) was determined with bioinformatics, western blot, and RIP assay. The hsa_circ_0078136 expression was reduced in RB tumor samples and cells. Additionally, its overexpression restricted the oncogenic properties of RB cells in vitro. Moreover, hsa_circ_0078136 overexpression lowered the protein levels of cytokine ligand molecules of IL-17 signaling pathway in RB cell lines. In vivo, hsa_circ_0078136 overexpression in subcutaneous tumor xenografts reduced tumor growth. We also observed that EIF4A3 binds to the downstream flanking sequence of hsa_circ_0078136 in the SHRPH pre-mRNA transcript, and EIF4A3 overexpression reduced hsa_circ_0078136 expression, suggesting that EIF4A3 inhibited hsa_circ_0078136 formation. Our results demonstrate that hsa_circ_0078136 is regulated by EIF4A3 and functions as a tumor suppressor via the IL-17 signaling pathway in RB.

Chen M ，He H ，Cheng H ，Zhang G ... -  《-》

EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway.

Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients' TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3). Hsa_circ_0001165 acts as a miRNA sponge for miR-381-3p, increasing the expression of tensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches.

Zhang X ，Bian Y ，Li Q ，Yu C ，Gao Y ，Tian B ，Xia W ，Wang W ，Xin L ，Lin H ，Wang L ... -  《-》

EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway.

Circular RNAs (circRNAs) have garnered attention for their potential involvement in the regulation of cellular aging processes. Exploring the role and mechanism of circRNAs in cellular senescence may help to identify new anti-aging therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0127071 in renal aging. We employed high-throughput sequencing to assess circRNA expression differences in kidney tissues from young and old groups. qRT-PCR confirmed that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Cellular senescence was evaluated using SA-β-Gal staining and Masson's trichrome staining. Using RNA Immunoprecipitation (RIP), RNA Pull-Down Assay (RNA pull down), and Western Blot (WB) to study the interaction between hsa_circ_0127071 and aging related pathway proteins. In this study, we found that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Silencing of EIF4A3, a protein involved in the JAK2/STAT5 signaling pathway, was found to delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by Erythropoietin (EPO) processing, and the senescence of Human glomerular mesangial cells (HGMCs) increased. After treatment with Losartan (LOS), the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings demonstrate that hsa_circ_0127071 promotes renal aging through the EIF4A3/JAK2/STAT5 signaling axis, highlighting a novel potential therapeutic target for the management of renal aging and associated disorders.

Chen Y ，Zhu X ，Sun D ，Yao L ，Yang S ，Wang L ... -  《Scientific Reports》

EIF4A3-Induced Circ_0059914 Promoted Angiogenesis and EMT of Glioma via the miR-1249/VEGFA Pathway.

Gliomas are common brain tumors. Despite extensive research, the 5-year survival rate of glioma remains low. Many studies have reported that circular RNAs (circRNAs) play a role in promoting the malignant progression of glioma; however, the role of circ_0059914 in this process remains unclear. In this study, we aimed to investigate the function and underlying mechanism of circ_0059914 in glioma. Western blotting and qRT-PCR were used to determine the levels of circ_0059914, miR-1249, VEGFA, N-cadherin, vimentin, Snail, and EIF4A3. EDU and colony formation assays were conducted to evaluate cell proliferation. Transwell assays were used to explore cell migration and invasion and tube formation assays were used to analyze angiogenesis. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were used to explore the relationship between EIF4A3, circ_0059914, miR-1249, and VEGFA. A xenograft tumor assay was performed to determine the role of circ_0059914 in vivo. Circ_0059914 expression was upregulated in gliomas. Knockdown of gliomal circ_0059914 expression reduced the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, and growth of glioma cells in vivo. Circ_0059914 sponged miR-1249, and miR-1249 inhibition reversed the circ_0059914 knockdown-mediated effects in glioma cells. VEGFA was found to be a target gene of miR1249; overexpression of VEGFA reversed the effect of miR-1249 up-regulation in glioma. Finally, EIF4A3 increased the expression of circ_0059914. EIF4A3-induced circ_0059914 expression plays a role in promoting glioma via the miR-1249/VEGFA axis.

Yu W ，Chen D ，Ma L ，Lin Y ，Zheng J ，Li X ... -  《-》

hsa_circ_0021727 facilitates esophageal squamous cell carcinoma progression by stabilizing GBX2 mRNA through interacting with EIF4A3.

Lin J ，Zhu Q ，Zeng F 《NEOPLASMA》