Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals

Xue, Dingwei; Wang, Huan; Chen, Yuanlei; Shen, Danyang; Lu, Jinmei; Wang, Mingchao; Zebibula, Abudureheman; Xu, Liwei; Wu, Haiyang; Li, Gonghui; Xia, Liqun

doi:10.1186/s12943-019-1072-5

Cited by 136 publications

(120 citation statements)

References 47 publications

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“…Before the present study, various studies demonstrated that miRNAs such as hsa-miR-137 [54,55], hsa-mir-211-5p [56], hsa-mir-224-5p [57], hsa-miR-335-5p [58], and hsa-mir-296-3p [59], are involved in the regulation of RCC progression. In addition, increased hsa-miRNA-9 and decreased hsa-miRNA-200a could serve as biomarkers for distinguishing hemangioblastomas from metastatic clear cell RCC [60].…”

Section: Discussionmentioning

confidence: 65%

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics

et al. 2020

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The survival rate in patients with metastatic renal cell carcinoma (RCC) is low. In addition, metastatic RCC resists traditional treatment. Therefore, identification of novel biomarkers, signaling pathways, and therapeutic targets is an important issue. The aim of the present study is to identify novel prognostic markers from the miRNA-mediated network for the regulation of metastasis of RCC. To address this issue, the RNA of human RCC cell lines, 786-O and ACHN, derived from primary and metastatic sites, respectively, were collected and subjected to RNA sequencing and small RNA sequencing. The bioinformatic analysis revealed that the pathways of the genes with different expressions were related to tumor progression, and identified miRNA and miRNA-long non-coding RNA (lncRNA) interactions, and mRNA. The results revealed that the expressions of seven miRNAs were associated with the overall survival rate of patients with RCC. Furthermore, the expressions of two lncRNA and three protein-coding genes (mRNA) were significantly associated with the increased or decreased disease-free survival rate. Although the detailed regulatory mechanism between miRNAs and targeted genes was not fully understood, our findings present novel prognostic markers and novel insight on miRNA-mediated pathways for metastatic RCC.

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Section: Discussionmentioning

confidence: 65%

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics

et al. 2020

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“…We [27]. Differentially, circ-AKT3 overexpression was demonstrated to decrease migrated and invaded CCRCC cells [28]. CircRNA cRAPGEF5 [29] and has_circ_0072309 [30] also impeded tumor growth and metastasis in CCRCC.…”

Section: Discussionmentioning

confidence: 91%

Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2

Cheng

Cao

et al. 2020

Preprint

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Background Clear cell renal cell carcinoma (CCRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for CCRCC. This research aims to disclose the involvement of circRNA ribosomal protein L23a (circ_RPL23A) in CCRCC, and how it regulates carcinogenesis. Methods We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cellular behavior detection included cell cycle, proliferation, apoptosis and metastasis, which were severally analyzed using propidium iodide (PI)-flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), Annexin V/PI-flow cytometry and transwell migration/invasion assays. ACAT2 and related proteins of cell cycle, epithelial-mesenchymal transition (EMT) were measured via western blot. Target relationship was analyzed via dual-luciferase reporter assay. A xenograft model was used to study circ_RPL23A action in mice. Results Both in CCRCC tissues and cells, circ_RPL23A had a down-regulated tendency. Explicitly, circ_RPL23A overexpression inhibited cell cycle, proliferation and metastasis but enhanced apoptosis of CCRCC cells, whereas these effects of circ_RPL23A were dependent on the suppression of its target miR-1233. Besides, miR-1233 could target ACAT2 and circ_RPL23A regulated ACAT2 by sponging miR-1233. Also importantly, miR-1233 was a pro-cancer gene in CCRCC via targeting ACAT2. CCRCC tumor growth was also decreased in vivo by circ_RPL23A through miR-1233/ACAT2 axis. Conclusion Altogether, the circ_RPL23A/miR-1233/ACAT2 axis in this report provides an in-depth cognition for CCRCC pathogenesis and circ_RPL23A may has pivotal value in diagnosing and treating CCRCC.

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“…Increasing data have shown that a variety of organisms could generate circRNAs by back-splicing, including Drosophila [25], rice [26], silkworm [27], zebrafish [28], and humans [29]. In addition to cellular transcripts, viral transcripts were found to form circRNAs in KSHV-infected primary effusion lymphoma cells, EBV-infected cells [20,21] or HPV16 [23].…”

Section: Discussionmentioning

confidence: 99%

HBV pgRNA can generate a circRNA with two junction sites

Zhu

Liang

Pan

et al. 2020

Preprint

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To verify whether Hepatitis B virus (HBV) can form circRNA, the circRNA sequencing results of the HBV-positive HepG 2.2.15 hepatocarcinoma cell line were compared with the HBV genome. A novel circRNA, named as HBV_circ_1, was mapped to the 489-2985 nt region of the HBV genome (GenBank accession No. KU668446.1), which was derived from HBV pgRNA and has two junction sites. A partial fragment of the pgRNA (corresponding to HBV DNA genome 489-3,182-2,985nt) was resected and then connected to form a junction site of HBV_circ_1 (corresponding to HBV DNA genome 489/2985nt). The 5′-terminal region (corresponding to HBV DNA genome 1,820-1,932nt) of pgRNA was repeated with the region of pgRNA at the 3′-terminal region. Another junction site of HBV_circ_1 (corresponding to HBV DNA genome 1820nt) was formed in a manner similar to DNA homologous recombination mediated by repeats of pgRNA. Moreover, this RNA homologous recombination mediated by the repeats of pgRNA does not have tissue specificity and genus specificity. Reverse transcription PCR, northern blotting, and tissue in situ hybridization confirmed the existence of HBV_circ_1 in HepG2.2.15 cells and HBV related hepatocellular carcinoma (HCC) tissue. This study expands our understanding of circRNA generation mechanisms, and provide a new perspective for understanding the molecular pathogenesis of the virus.

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Circ-AKT3 inhibits clear cell renal cell carcinoma metastasis via altering miR-296-3p/E-cadherin signals

Cited by 136 publications

References 47 publications

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics

Identification of the Potential Prognostic Markers from the miRNA-lncRNA-mRNA Interactions for Metastatic Renal Cancer via Next-Generation Sequencing and Bioinformatics

Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2

HBV pgRNA can generate a circRNA with two junction sites

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