Dataset Information

Circular RNA hsa_circ_001350 contributes to osteosarcoma progression by regulating microRNA-578/CCR4-NOT transcription complex and subunit 7/Wnt signaling.

ABSTRACT: Accumulating evidence has revealed that circular RNAs (circRNAs) play important roles in cancer by sponging microRNAs (miRNAs). A previous study has shown that hsa_circ_001350 expression is increased in glioma tissue samples and cells and that hsa_circ_001350 directly sponges miR-1236. Here, we investigated the role of hsa_circ_001350 in osteosarcoma (OS). Bioinformatics analysis was performed to examine the potential interactions among hsa_circ_001350, miR-578, and the CCR4-NOT transcription complex and subunit 7 (CNOT7). Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyze gene expression and protein levels, respectively. Hsa_circ_001350 expression was upregulated in OS tissues and cell lines. The deletion of hsa_circ_001350 inhibited the proliferation, migration, and invasion of OS cells. The downregulation of hsa_circ_001350 suppressed CNOT7 expression by sponging miR-578 as confirmed by rescue experiments and luciferase reporter assays. Specifically, the depletion of hsa_circ_001350 inhibited the protein expression of β-catenin, cyclin D1, and c-myc in OS cells, and CNOT7 overexpression reversed this effect. We conclude that hsa_circ_001350 contributes to OS progression by regulating miR-578/CNOT7/Wnt signaling. Thus, hsa_circ_001350, miR-578, and CNOT7 may be potential targets for the treatment of OS.

SUBMITTER: Xu R

PROVIDER: S-EPMC10326583 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Circular RNA hsa_circ_001350 contributes to osteosarcoma progression by regulating microRNA-578/CCR4-NOT transcription complex and subunit 7/Wnt signaling.

Xu Rujin R Ci Xingyuan X He Fang F Chen Yueqin Y

American journal of cancer research 20230615 6

Accumulating evidence has revealed that circular RNAs (circRNAs) play important roles in cancer by sponging microRNAs (miRNAs). A previous study has shown that hsa_circ_001350 expression is increased in glioma tissue samples and cells and that hsa_circ_001350 directly sponges miR-1236. Here, we investigated the role of hsa_circ_001350 in osteosarcoma (OS). Bioinformatics analysis was performed to examine the potential interactions among hsa_circ_001350, miR-578, and the CCR4-NOT transcription co ...[more]

PMID: 37424831

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Project description:BackgroundCircular RNAs (circRNAs) have emerged as a novel category of non-coding RNA, which exhibit a pivotal effect on regulating gene expression and biological functions, yet how circRNAs function in osteosarcoma (OSA) still demands further investigation. This study aimed at probing into the function of hsa_circ_0000282 in OSA.MethodsThe expressions of circ_0000282 and miR-192 in OSA tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of circ_0000282 and clinicopathological features of OSA patients was analyzed. The expressions of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in OSA cells were assayed by Western blot. The proliferation and apoptosis of OSA cells were examined by CCK-8, BrdU and flow cytometry, respectively. Bioinformatics analysis, dual-luciferase reporter gene assay and RIP experiments were employed to predict and validate the targeting relationships between circ_0000282 and miR-192, and between miR-192 and XIAP, respectively.ResultsCirc_0000282 was highly expressed in OSA tissues and cell lines, which represented positive correlation with Enneking stage of OSA patients and negative correlation with tumor differentiation degree. In vitro experiments confirmed that overexpression of circ_0000282 markedly facilitated OSA cell proliferation and repressed cancer cell apoptosis in comparison to control group. Besides, knockdown of circ_0000282 repressed OSA cell proliferation and promoted apoptosis. Additionally, the binding relationships between circ_0000282 and miR-192, and between miR-192 and XIAP were validated. Circ_0000282 indirectly up-regulated XIAP expression by adsorbing miR-192, thereby playing a role in promoting cancer in OSA.ConclusionCirc_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.

Project description:Background:Osteosarcoma (OS) is the most common primary malignancy of bone with a high incidence in children. Circular RNAs (circRNAs) play crucial roles in the carcinogenesis and chemoresistance of OS. In the current work, we focused on the function and mechanism of hsa_circ_0003496 (circ_0003496) in OS progression and chemoresistance. Materials and Methods:The expression levels of circ_0003496, miR-370 and Krüppel-like factor 12 (KLF12) mRNA were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell Counting Kit-8 (CCK-8) assay was used to assess the 50% inhibitory concentration (IC50) value and cell proliferation. Cell migration, invasion and apoptosis were detected by transwell assay and flow cytometry, respectively. Western blot analysis was performed to assess the protein level. Targeted relationships among circ_0003496, miR-370 and KLF12 were validated by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Animal studies were carried out to observe the role of circ_0003496 in vivo. Results:Our results indicated that circ_0003496 up-regulation was associated with doxorubicin (DXR) resistance of OS. Circ_0003496 knockdown repressed DXR-resistant OS cell proliferation, migration and invasion, and enhanced apoptosis and DXR sensitivity. Circ_0003496 functioned as a sponge of miR-370, and miR-370 mediated the regulatory effect of circ_0003496 depletion on DXR-resistant OS cell progression and DXR sensitivity. KLF12 was a direct target of miR-370, and miR-370 overexpression suppressed cell progression and enhanced DXR sensitivity by KLF12. Moreover, circ_0003496 protected against KLF12 repression through sponging miR-370. Additionally, circ_0003496 knockdown hampered tumor growth and promoted DXR sensitivity in vivo. Conclusion:Our present work suggested that the knockdown of circ_0003496 suppressed OS progression and enhanced DXR sensitivity at least partially through modulating KLF12 expression via functioning as a miR-370 sponge, highlighting new opportunities for OS management.

Project description:An important factor in the emergence and progression of osteosarcoma (OS) is the dysregulated expression of microRNAs (miRNAs). Transcription factor 7-like 1 (TCF7L1), a member of the T cell factor/lymphoid enhancer factor (TCF/LEF) transcription factor family, interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein. This study sought to elucidate the impact of the interaction between miR-329-3p and TCF7L1 on the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches. MiR329-3p was significantly downregulated, while TCF7L1 was considerably up-regulated in all examined OS cell lines. Additionally, a clinical comparison study was performed using the TCGA database. Subsequently, the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments. When miR-329-3p was transfected into the OS cell line, the expression of TCF7L1 decreased, the proliferation of OS cells was inhibited, the cytoskeleton disintegrated, and the nucleus condensed to form apoptotic bodies. The expression of proteins that indicate apoptosis increased simultaneously. The cell cycle was arrested in the G0/G1 phase, and the G1/S transition was blocked. The introduction of miR-329-3p also inhibited downstream Cyclin D1 of the Wnt pathway. Xenograft experiments indicated that the overexpression of miR-329-3p significantly inhibited the growth of OS xenografts in nude mice, and the expression of TCF7L1 and c-Myc in tumor tissues decreased. MiR-329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo. Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7L1 by miR-329-3p. Summarizing these results, it can be inferred that miR-329-3p exerts anticancer effects in osteosarcoma by inhibiting TCF7L1.

Dataset Information

Circular RNA hsa_circ_001350 contributes to osteosarcoma progression by regulating microRNA-578/CCR4-NOT transcription complex and subunit 7/Wnt signaling.

Publications

Circular RNA hsa_circ_001350 contributes to osteosarcoma progression by regulating microRNA-578/CCR4-NOT transcription complex and subunit 7/Wnt signaling.

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