Circ_0072088 promotes breast carcinoma progression via modulating miR-607/RNF2 axis.

OBJECTIVES: To explore how the circular non-coding RNA circ_0072088 influences the progression of breast carcinoma (BC) by affecting cell behavior. METHODS: We measured the levels of circ_0072088, microRNA-607 (miR-607), and ring finger protein 2 (RNF2) mRNA levels in BC tissues and cell lines using quantitative real-time PCR. We also conducted cell counting kit-8 (CCK-8), BrdU incorporation, and flow cytometry assays to assess cell viability, cell cycle, and apoptosis, respectively. RESULTS: We observed increased levels of circ_0072088 and RNF2, and decreased levels of miR-607 in BC tissues. Overexpressing circ_0072088 promoted BC cell proliferation and cell cycle progression while inhibiting apoptosis. Conversely, silencing circ_0072088 had the opposite effects. Our data suggest that circ_0072088 directly targets and downregulates miR-607, which in turn upregulates RNF2, a target of miR-607. Moreover, miR-607 overexpression could mitigate the pro-proliferative and anti-apoptotic effects of circ_0072088 on BC cells. CONCLUSION: Circ_0072088 drives BC progression by downregulating miR-607 and upregulating RNF2, thereby promoting cell proliferation and cycle progression while reducing apoptosis.

Circular non-coding RNA circ_0072088 serves as a ceRNA, targeting the miR-1225-5p/WT1 axis to regulate non-small cell lung cancer cell malignant behavior.

BACKGROUND: Circular RNA (circRNA) circ_0072088 has been reported to be associated with NSCLC cell growth, migration, and invasion. However, the role and mechanism of circ_0072088 on NSCLC development have not yet been determined. METHODS: Circ_0072088, microRNA-1225 (miR-1225-5p), and Wilms' tumor (WT1) suppressor gene level was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Migration, invasion, and apoptosis were detected using transwell and flow cytometry assays. Matrix metallopeptidase 9 (MMP9), hexokinase 2 (HK2), and WT1 were examined using western blot assay. The biological role of circ_0072088 on NSCLC tumor growth was examined by the xenograft tumor model in vivo. Circular RNA Interactome and TargetScan were used to predict the binding between miR-1225-5p and circ_0072088 or WT1, followed by confirmation using a dual-luciferase reporter. RESULTS: Circ_0072088 and WT1 were highly expressed in NSCLC tissues and cells, and miR-1225-5p was decreased. Knockdown of circ_0072088 might repress migration, invasion, and glycolysis, and facilitate apoptosis of NSCLC cells in vitro. Circ_0072088 silencing also blocked NSCLC tumor growth in vivo. Mechanistically, circ_0072088 acted as a sponge of miR-1225-5p to regulate WT1 expression. CONCLUSION: Circ_0072088 knockdown could inhibit cell growth, migration, invasion, and glycolysis partially by regulating the miR-1225-5p/WT1 axis, thus providing a promising therapeutic target for NSCLC treatment.

Circ_0072088 knockdown contributes to cisplatin sensitivity and inhibits tumor progression by miR-944/LASP1 axis in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is an aggressive tumor that accounts for a large proportion of cancer-related deaths. Cisplatin (CDDP) has been utilized to treat NSCLC. However, the efficacy of CDDP is usually restrained owing to the development of drug resistance. This study aims to reveal the molecular mechanism of the resistance of NSCLC cells to CDDP. METHODS: The expression levels of circRNA_0072088 (circ_0072088), microRNA-944 (miR-944), and LIM and SH3 protein 1 (LASP1) were measured by quantitative real-time PCR (qRT-PCR) in CDDP-resistant NSCLC tissues and cells. Protein expression was determined by Western blotting in CDDP-resistant NSCLC tissues and cells. The functional effects of circ_0072088, miR-944, and LASP1 on CDDP sensitivity and NSCLC progression were revealed by Cell Counting Kit-8 (CCK-8), flow cytometry, cell colony formation, wound healing, and transwell invasion assays. The binding relationship between miR-944 and circ_0072088 or LASP1 was identified by a dual-luciferase reporter and RNA immunoprecipitation assay. The effects of circ_0072088 knockdown on tumor growth in vivo were analyzed by an in vivo tumor formation assay. RESULTS: Circ_0072088 and LASP1 expression were significantly upregulated, while miR-944 expression was downregulated in CDDP-resistant NSCLC tissues and cells as compared with control groups. Circ_0072088 expression was significantly associated with tumor-node-metastasis stage and tumor size. Functionally, circ_0072088 knockdown improved CDDP sensitivity and repressed NSCLC cell malignancy, whereas miR-944 inhibitor hindered these effects. Mechanistically, circ_0072088 functioned as a sponge for miR-944 and miR-944 targeted LASP1. Circ_0072088 knockdown improved the sensitivity of tumor to CDDP in vivo. CONCLUSION: Circ_0072088 silencing improved CDDP sensitivity and inhibited NSCLC progression by downregulating LASP1 expression through sponging miR-944. These data provide novel insight into the resistance of NSCLC to CDDP.

Circ_0072008, an oncogene in pancreatic ductal adenocarcinoma, contributes to tumour cell malignant progression and glycolysis by regulating miR-545-3p/SLC7A11 axis.

BACKGROUND: The hsa_circRNA_103809 (circ_0072088) has been an emerging tumour regulator in human cancers, and is identified as one most aberrantly expressed circRNA in patients with pancreatic ductal adenocarcinoma (PDAC). However, the role of circ_0072088 remains unclear in PDAC cells. METHODS: Expression of circ_0072088, microRNA (miR)-545-3p and solute carrier family 7 member 11 (SLC7A11) was detected by real-time quantitative PCR and western blotting. Cell progression was measured by cell counting kit (CCK)-8 assay, transwell assays and flow cytometry, as well as xenograft tumour models. Glycolysis was evaluated by commercial assay kits. The interaction among circ_0072088, miR-545-3p and SLC7A11 was confirmed by dual-luciferase reporter assay. RESULTS: Circ_0072088 was upregulated in PDAC tumours and cells; besides, high circ_0072088 level was associated with high tumour-node-metastasis (TNM) stage. The circ_0072088 siRNA suppressed cell viability, migration, invasion, extracellular acidification rate (ECAR), lactate production, glucose uptake, and ATP generation, but promoted apoptosis rate and oxygen consumption rate (OCR) in SW1990 and PANC-1 cells. In vivo, circ_0072088 knockdown retarded tumour growth of PANC-1 cells. Overexpressing miR-545-3p mimicked circ_0072088 siRNA-induced actions, and inhibited cell progression and glycolysis of SW1990 and PANC-1 cells. Moreover, SLC7A11 downregulation could be mediated by both circ_0072008 siRNA and miR-545-3p mimic, and participating in suppressive role in cell progression and glycolysis of SW1990 and PANC-1 cells. In mechanism, miR-545-3p was targeted by circ_0072008, and SLC7A11 was target of miR-545-3p. CONCLUSION: Circ_0072088 elicited oncogenic role in malignant cell progression and glycolysis of PDAC cells through circ_0072088/miR-545-3p/SLC7A11 pathway.HighlightsCirc_0072088 was upregulated in PDAC tumours and was associated with high tumour burden.Blocking circ_0072088 suppressed cell proliferation, migration, invasion, and glycolysis in PDAC cells.Circ_0072088 could directly regulate miR-545-3p, and SLC7A11 was a target of miR-545-3p.Restoring miR-545-3p mimicked the effects of circ_0072088 knockdown in PDAC cell in vitro.

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16.

Background: Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC). Methods: Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells. Results: The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC. Conclusion: Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.

Circ_0072088 promotes progression of hepatocellular carcinoma by activating JAK2/STAT3 signaling pathway via miR-375.

Circular RNAs feature prominently in cancer development. Nonetheless, the role of circ_0072088 in hepatocellular carcinoma (HCC) remains unclear. GEO databases (GSE97332, GSE108724, GSE36915, and GSE33006) were used to screen out the differentially expressed circRNAs, miRNAs, and mRNA in HCC. The expressions of circ_0072088, miR-375, and Janus Kinase 2 (JAK2) mRNA in HCC tissue and cell lines were determined with quantitative real-time polymerase chain reaction. RNase R treatment assay was used to measure the stability of circ_0072088, and subcellular fraction assay was used to detect the localization of circ_0072088. Cell counting kit-8 assay, flow cytometry, and Transwell assay were used to measure proliferation, apoptosis, migration, and invasion of HCC cells. RNA immunoprecipitation and dual-luciferase reporter gene assay were employed for investigating the binding sequence between circ_0072088 and miR-375, as well as miR-375 and JAK2 3'UTR. Western blot assay was used to detect the expression of JAK2 and p-STAT3 after circ_0072088 and miR-375 were selectively regulated. Circ_0072088 and JAK2 mRNA expressions were highly expressed in HCC tissues and cell lines while miR-375 expression was remarkably downregulated. Circ_0072088 was resistant to RNase R treatment and mainly located in the cytoplasm of HCC cells. The transfection of circ_0072088 overexpression plasmid or miR-375 inhibitors promoted the proliferation, migration, and invasion, and inhibited the apoptosis of HCC cells, whereas transfection of circ_0072088 siRNA or miR-375 mimics exerted opposite effects. Besides, miR-375 was confirmed as a target of circ_0072088 and miR-375 could further downregulate the expression of JAK2. MiR-375 mimics could reverse the upregulation of JAK2 and p-STAT3 protein induced by circ_0072088 overexpression. Circ_0072088 can enhance the proliferation, migration, and invasion, and impede apoptosis of HCC cells. Mechanistically, circ_0072088 activates JAK2/STAT3 signaling pathway by serving as a molecular sponge of miR-375.

Circ_0072088 promotes the development of non-small cell lung cancer via the miR-377-5p/NOVA2 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death globally. This study aimed to disclose the role of circular RNA circ_0072088 in NSCLC and illustrate its potential mechanism. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0072088, zinc finger RNA binding protein (ZFR), microRNA-377-5p (miR-377-5p) and NOVA alternative splicing regulator 2 (NOVA2). The viability, colony formation, cell cycle, migration and invasion of NSCLC cells were measured by cell counting kit-8 (CCK8) assay, colony formation assay, flow cytometry, wound healing assay and transwell invasion assay. Western blot assay was employed to examine the protein levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, matrix metallopeptidase 2 (MMP2), MMP9 and NOVA2. The downstream targets of circ_0072088 and miR-377-5p were searched through using circular RNA Interactome and TargetScan databases, and the interaction between miR-377-5p and circ_0072088 or NOVA2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. in vivo tumor growth assay was used to evaluate the functions of circ_0072088 in the progression of NSCLC in vivo. RESULTS: GSE101586 dataset and the analysis of tissue specimens showed that circ_0072088 was aberrantly upregulated in tumor tissues of lung cancer and NSCLC. Circ_0072088 interference caused marked suppression on the proliferation and motility of NSCLC cells. Circ_0072088 could negatively regulate miR-377-5p through direct combination. Circ_0072088 contributed to the progression of NSCLC through sponging miR-377-5p. MiR-377-5p could directly interact with NOVA2, and the overexpression of NOVA2 overturned miR-377-5p-mediated influence on NSCLC cells. Circ_0072088 facilitated the progression of NSCLC in vivo. CONCLUSIONS: Circ_0072088 facilitated the proliferation and metastasis of NSCLC cells through upregulating NOVA2 via functioning as a competitive endogenous RNA (ceRNA) for miR-377-5p.