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Overexpressed circRANBP17 acts as an oncogene to facilitate nasopharyngeal carcinoma via the miR-635/RUNX2 axis.

ABSTRACT: Circular RNAs (circRNAs) are implicated in the initiation and progress of several diseases, including cancer. However, the precise role of circRNAs in human nasopharyngeal carcinoma (NPC) remains unclear. In this research, we found a new circRNA hsa_circ_0001554 (circRANBP17), which was derived from the RAN binding protein 17 (RANBP17). Our qRT-PCR data found that circRANBP17 expression was up-regulated in NPC tissue and cells. Functional silencing studies revealed that circRANBP17 inhibited NPC cell proliferation and invasion in vitro, and circRANBP17 down-regulation also reduced tumor growth in nude mice. MiR-635 was demonstrated as a direct target of circRANBP17; circRANBP17 up-regulated RUNX2 expression levels by sponging miR-635, thereby promoting NPC proliferation and invasion. Thus, our data provide the evidence for the first time that circRANBP17 is a new onco-circRNA via miR-635/RUNX2 axis regulation, and may function as a novel therapeutic target for NPC treatment.

SUBMITTER: Zhou M

PROVIDER: S-EPMC8176428 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Overexpressed circRANBP17 acts as an oncogene to facilitate nasopharyngeal carcinoma via the miR-635/RUNX2 axis.

Zhou Minghui M Zhang Puwen P Zhao Yulin Y Liu Rui R Zhang Yujie Y

Journal of Cancer 20210519 14

Circular RNAs (circRNAs) are implicated in the initiation and progress of several diseases, including cancer. However, the precise role of circRNAs in human nasopharyngeal carcinoma (NPC) remains unclear. In this research, we found a new circRNA hsa_circ_0001554 (circRANBP17), which was derived from the RAN binding protein 17 (RANBP17). Our qRT-PCR data found that circRANBP17 expression was up-regulated in NPC tissue and cells. Functional silencing studies revealed that circRANBP17 inhibited NPC ...[more]

PMID: 34093832

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Project description:The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation.

Dataset Information

Overexpressed circRANBP17 acts as an oncogene to facilitate nasopharyngeal carcinoma via the miR-635/RUNX2 axis.

Publications

Overexpressed circRANBP17 acts as an oncogene to facilitate nasopharyngeal carcinoma via the miR-635/RUNX2 axis.

Similar Datasets

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