Dataset Information

CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression.

ABSTRACT: Circular RNA (circRNA) is shown to participate in various tumors, including lung cancer. Although a few circRNAs involved in lung cancer are reported, whether circRNA negatively regulates lung cancer development remains elusive. In this study, we showed hsa_circ_100395 expression was decreased in lung cancer tissues. Besides, hsa_circ_100395 level was inversely correlated with TNM stage and metastases in lung cancer and low hsa_circ_100395 expression in patients predicted poor prognosis. Overexpression of hsa_circ_100395 dramatically inhibited lung cancer cell proliferation, arrested cell-cycle progression and reduced cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_100395 overexpression delayed tumor growth in vivo. Mechanistically, we showed hsa_circ_100395 serves as a sponge for miR-1228 targeting TCF21 in lung cancer. Rescue assays indicated that hsa_circ_100395 regulates lung cancer cell proliferation, migration and invasion through modulating miR-1228/TCF21 pathway. Altogether, our study reveals a novel regulatory loop that hsa_circ_100395/miR-1228/TCF21 axis modulates lung cancer development. ABBREVIATIONS:circRNA: circular RNA; miRNA: microRNA; RNA-FISH: RNA fluorescence in situy bridization; qRT-PCR: Reverse transcription and quantitative real-time PCR.

SUBMITTER: Chen D

PROVIDER: S-EPMC6224268 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression.

Chen Daishi D Ma Wei W Ke Zhaoyang Z Xie Fei F

Cell cycle (Georgetown, Tex.) 20180913 16

Circular RNA (circRNA) is shown to participate in various tumors, including lung cancer. Although a few circRNAs involved in lung cancer are reported, whether circRNA negatively regulates lung cancer development remains elusive. In this study, we showed hsa_circ_100395 expression was decreased in lung cancer tissues. Besides, hsa_circ_100395 level was inversely correlated with TNM stage and metastases in lung cancer and low hsa_circ_100395 expression in patients predicted poor prognosis. Overexp ...[more]

PMID: 30176158

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Project description:BackgroundMultiple myeloma (MM) accounts for 10% of all hematological malignancies. Dysregulation of microRNAs (miRNAs) or long non-coding RNAs (lncRNAs) has important impacts on progression of MM. Circular RNAs (circRNAs) are correlated with malignancy in the modulation of tumor progression. This study aims to investigate the effect of circ_0000190 on regulating the progression of MM.MethodMicroscopic examination via single molecule fluorescent in situ hybridization indicates the location of circ_0000190. qRT-PCR and Western blot were used to evaluate the expression of RNAs and proteins. Potential target of circ_0000190 was searched as miRNA, and examined by luciferase reporter assay. A computational screen was also conducted to search the potential target of miRNA. In vitro cell viability, proliferation, apoptosis assays and flow cytometric were performed to assess the effects of circ_0000190 and its target on MM. Mice model of human MM was established with subcutaneous xenograft tumor, qRT-PCR and western blot were performed to detect the underlying mechanisms of circ_0000190 on MM.ResultsCirc_0000190 was located in the cytoplasm, and down-regulated in both bone marrow tissue and peripheral blood, while the target of circ_0000190, miR-767-5p, was up-regulated, suggesting a negative correlation between them. The binding ability between circ_0000190 and miR-767-5p was confirmed by luciferase reporter assay. Moreover, circ_0000190 inhibited cell viability, proliferation and induced apoptosis of MM thus inhibiting cell progression, which is partially through the negative regulation of miR-767-5p. Mitogen-activated protein kinase 4 (MAPK4) is a direct target of miR-767-5p. In addition, over-expression of miR-767-5p promoted cell progression by directly targeting and regulating MAPK4. The MM model mice with administration of circ_0000190 suppressed tumor growth and progression.ConclusionOur results revealed that the ability of circ_0000190 to protect against MM was inherited through repression of miR-767-5p, and miR-767-5p might be a tumor drive through targeting MAPK4. Therefore, a novel role of circ_0000190 on regulating the progression of MM was found, and the clinical application of circRNAs might represent a strategy in MM.

Project description:BackgroundHypoxia has been shown to induce the malignant progression of cancer, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) is considered to be an important regulator of cancer progression. However, the role of a newly discovered circRNA, circ_0000376, in the progression of NSCLC is unclear.MethodsThe relative expression levels of circ_0000376, miR-1182 and neuro-oncological ventral antigen 2 (NOVA2) were detected via quantitative real-time polymerase chain reaction (qRT-PCR). Glucose consumption and lactate production were determined using Glucose Assay Kit and Lactate Assay Kit, respectively. Moreover, the protein levels of glycolysis markers and NOVA2 were measured using Western blot (WB) analysis. Furthermore, 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to assess cell viability, and transwell assay was employed to evaluate cell migration and invasion. The interaction between miR-1182 and circ_0000376 or NOVA2 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, animal experiments were conducted to assess the influence of circ_0000376 silencing on NSCLC tumor growth in vivo.ResultsCirc_0000376 was upregulated in NSCLC, and its high expression was related to the poor overall survival of NSCLC patients. Hypoxia could enhance circ_0000376 expression and promote the glycolysis, viability, migration, and invasion of NSCLC cells. However, silencing of circ_0000376 could inhibit the glycolysis, viability, migration, and invasion of hypoxia-induced NSCLC cells. Additionally, circ_0000376 could sponge miR-1182, and miR-1182 could target NOVA2. MiR-1182 silencing could reverse the inhibitory effect of circ_0000376 knockdown on NSCLC progression, and NOVA2 overexpression also could reverse the suppressive effect of miR-1182 overexpression on NSCLC progression. Meanwhile, miR-1182 inhibitor could invert the negative regulation effect of circ_0000376 silencing on NOVA2 expression. In addition, circ_0000376 knockdown inhibited the NSCLC tumor growth via regulating the miR-1182 and NOVA2 expression in vivo.ConclusionCirc_0000376 promoted NSCLC progression by regulating the miR-1182/NOVA2 axis, suggesting that circ_0000376 might be a potential biomarker for NSCLC treatment.

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CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression.

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CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression.

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