CircVRK1 regulates tumor progression and radioresistance in esophageal squamous cell carcinoma by regulating miR-624-3p/PTEN/PI3K/AKT signaling pathway.

As a novel class of noncoding RNAs (ncRNAs), circular RNAs (circRNAs) have been verified to be potential biomarkers and therapeutic targets for human malignant tumors. However, the thorough understanding of circRNAs in the progression of esophageal squamous cell carcinoma (ESCC) still needs to be improved. This study focused on exploring the function and mechanism of circVRK1 in ESCC. At first, we examined the expression level of circVRK1 in ESCC tissues and cell lines with qRT-PCR. We found that circVRK1 was downregulated in ESCC tissues and cell lines. Kaplan-Meier method was used to analyze the correlation between circVRK1 expression and the overall survival of ESCC patients. Functionally, overexpression of circVRK1 suppressed the cell proliferation, migration and epithelial-mesenchymal transition (EMT) and reversed the radioresistance. Therefore, we identified the tumor suppressive role of circVRK1 in ESCC progression. Mechanistically, circVRK1 positively regulated PTEN by acting as a molecular sponge of miR-624-3p. Moreover, circVRK1 decreased the activity of PI3K/AKT signaling pathway by upregulating PTEN. Rescue assays were carried out to confirm the function of circVRK1-miR-624-3p-PTEN axis in ESCC progression. Our findings showed that circVRK1 suppressed ESCC progression by regulating miR-624-3p/PTEN axis and PI3K/AKT signaling pathway, suggesting the potential therapeutic value of circVRK1 for ESCC.

He Y ，Mingyan E ，Wang C ，Liu G ，Shi M ，Liu S ... -  《-》

Circular RNA VRK1 facilitates pre-eclampsia progression via sponging miR-221-3P to regulate PTEN/Akt.

Pre-eclampsia (PE) is a worldwide pregnancy-related disorder. It is mainly characterized by defect migration and invasion of trophoblast cells. Recently, circular RNAs (circRNAs) have been believed to play a vital role in PE. The expression patterns and the biological functions of circRNAs in PE remain elusive. Here, we performed a circRNA microarray to identify putative PE-related circRNAs. Bioinformatics analyses were used to screen the circRNAs which have potential relationships with pre-eclampsia, and we identified a novel circRNA (circVRK1) that was up-regulated in PE placenta tissues. By using HTR-8/SVneo cells, circVRK1 knockdown significantly enhanced cell migration and invasion abilities, as well as epithelial-mesenchymal transition (EMT). Mechanistically, we found that circVRK1 and PTEN could function as the ceRNAs to miR-221-3p. Overexpression of miR-221-3p promoted cell migration, invasion and EMT via regulating PTEN. The cotransfection of miR-221-3p inhibitor or PTEN reversed the effect from circVRK1 knockdown. Moreover, the circVRK1/miR-221-3p/PTEN axis greatly regulated Akt phosphorylation. In general, circVRK1 suppresses trophoblast cell migration, invasion and EMT, by acting as a ceRNA to miR-221-3p to regulate PTEN, and further inhibit PI3K/Akt activation. The purpose of this paper is to open wide insights to investigate the onset of PE and provide new potential therapeutic targets in PE.

Li Z ，Zhou X ，Gao W ，Sun M ，Chen H ，Meng T ... -  《-》

Hsa_circ_0023984 Regulates Cell Proliferation, Migration, and Invasion in Esophageal Squamous Cancer via Regulating miR-1294/PI3K/Akt/c-Myc Pathway.

Circular RNAs (circRNAs) exert an essential function in the tumorigenesis and progression of esophageal squamous cancer (ESCC). Nonetheless, the role and potential mechanism of circ_0023984 in ESCC are blurred. circRNA expression profile data from Gene Expression Omnibus (GEO) database was applied to analyze circRNAs that were differentially expressed between ESCC tissues and paracancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze circ_0023984 expression and miR-1294 expression in ESCC tissues and cells. Then a series of functional experiments were executed to validate the role of circ_0023984 and miR-1294 in modulating the proliferation, migration, invasion, and cell cycle progression of ESCC cells. Luciferase reporter experiment was performed to confirm the targeting relationship between circ_0023984 and miR-1294. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out with DAVID database. Western blot assay was utilized to detect phosphorylated-Akt (p-Akt) expression and c-Myc expression. circ_0023984 was remarkably upmodulated in ESCC tumor tissues and cell lines. circ_0023984 overexpression was correlated with advanced clinical stage and lymph node metastasis of ESCC patients. circ_0023984 overexpression remarkably enhanced ESCC cell proliferation, migration, invasion, and cell cycle progression, while knockdown of circ_0023984 showed the opposite effect. circ_0023984 was the molecular sponge of miR-1294. miR-1294 could significantly inhibit ESCC cell proliferation, migration, invasion, and induce cell cycle arrest at G0/G1 phase. circ_0023984 affected ESCC progression through regulating miR-1294 expression. The target genes of miR-1294 were associated with cell cycle arrest and PI3K-Akt signaling pathway. circ_0023984 upregulated the expression of p-Akt and c-Myc by repressing miR-1294. circ_0023984 facilitates the malignant biological behaviors of ESCC cells through inhibiting miR-1294 and activating PI3K/Akt/c-myc pathway.

Liang W ，Wang C ，Wang J ，Zhang M ... -  《-》

lncTUG1/miR-144-3p affect the radiosensitivity of esophageal squamous cell carcinoma by competitively regulating c-MET.

Wang P ，Yang Z ，Ye T ，Shao F ，Li J ，Sun N ，He J ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

MiR-130b plays an oncogenic role by repressing PTEN expression in esophageal squamous cell carcinoma cells.

Yu T ，Cao R ，Li S ，Fu M ，Ren L ，Chen W ，Zhu H ，Zhan Q ，Shi R ... -  《BMC CANCER》