Dataset Information

Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP.

ABSTRACT: Prostate cancer (PCa) is one of the major men's malignancies with high mortality worldwide. Circular RNAs (circRNAs) have been shown to serve as essential regulators in human cancers. CircRNA can exert their functions by cooperating with their host genes. In the present study, microarray analysis revealed an upregulated mRNA in PCa samples. X-linked inhibitor of apoptosis protein (XIAP), a key regulator in the progression of human cancers. Through bioinformatics analysis, we determined that XIAP is a host gene for circRNA0005276. Therefore, this study focused on the interaction between circ0005276 and XIAP as well as their functions in PCa progression. The upregulation of XIAP and circ0005276 was determined in PCa tissues and cell lines. Moreover, we confirmed the positive regulation of circ0005276 on XIAP expression. Functionally, we validated that circ0005276 and XIAP promoted cell proliferation, migration and epithelial-mesenchymal transition. Mechanistically, we verified that circ0005276 interacted with FUS binding protein (FUS) so as to activate the transcription of XIAP. Rescue assays were conducted to determine the crucial role of XIAP in circ0005276 and FUS-mediated PCa cellular processes. Collectively, our study revealed the mechanism and function of circ0005276 and its host gene XIAP in PCa progression.

SUBMITTER: Feng Y

PROVIDER: S-EPMC6797747 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP.

Feng Yang Y Yang Yuxuan Y Zhao Xiaodan X Fan Yameng Y Zhou Long L Rong Jie J Yu Yan Y

Cell death & disease 20191017 11

Prostate cancer (PCa) is one of the major men's malignancies with high mortality worldwide. Circular RNAs (circRNAs) have been shown to serve as essential regulators in human cancers. CircRNA can exert their functions by cooperating with their host genes. In the present study, microarray analysis revealed an upregulated mRNA in PCa samples. X-linked inhibitor of apoptosis protein (XIAP), a key regulator in the progression of human cancers. Through bioinformatics analysis, we determined that XIAP ...[more]

PMID: 31624242

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Project description:Pulmonary arterial hypertension is a progressive and fatal disease. Recent studies suggest that circular RNA (circRNAs/circs) can regulate various biological processes, including cell proliferation. Therefore, it is possible that circRNA may have important roles in pulmonary artery smooth muscle cell proliferation in hypoxic pulmonary hypertension (HPH). The aim of the present study was to determine the role and mechanism of circRNA‑glutamate metabotropic receptor 1 (circ‑Grm1; mmu_circ_0001907) in pulmonary artery smooth muscle cell (PASMC) proliferation and migration in HPH. High‑throughput transcriptome sequencing was used to screen circRNAs and targeted genes involved in HPH. Cell Counting Kit‑8 (CCK‑8), 5‑ethynyl‑2‑deoxyuridine and wound healing assays were employed to assess cell viability and migration. Reverse transcription‑quantitative PCR and western blotting were used to detect target gene expression in different groups. Bioinformatical approaches were used to predict the interaction probabilities of circ‑Grm1 and Grm1 with FUS RNA binding protein (FUS). The interactions of circ‑Grm1, Grm1 and FUS were evaluated using RNA silencing and RNA immunoprecipitation assays. The results demonstrated that circ‑Grm1 was upregulated in hypoxic PASMCs. Further experiments revealed that the knockdown of circ‑Grm1 could suppress the proliferation and migration of hypoxic PASMCs. Transcriptome sequencing revealed that Grm1 could be the target gene of circ‑Grm1. It was found that circ‑Grm1 could competitively bind to FUS and consequently downregulate Grm1. Moreover, Grm1 could inhibit the function of circ‑Grm1 by promoting the proliferative and migratory abilities of hypoxic PASMCs. The results also demonstrated that circ‑Grm1 influenced the biological functions of PASMCs via the Rap1/ERK pathway by regulating Grm1. Overall, the current results suggested that circ‑Grm1 was associated with HPH and promoted the proliferation and migration of PASMCs via suppression of Grm1 expression through FUS.

Project description:BACKGROUND:Circular 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. METHODS:The 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. RESULTS:Circ_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. CONCLUSION:Circ_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.

Dataset Information

Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP.

Publications

Circular RNA circ0005276 promotes the proliferation and migration of prostate cancer cells by interacting with FUS to transcriptionally activate XIAP.

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