Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

Mo, Yongzhen; Wang, Yumin; Wang, Yian; Deng, Xiaolei; Yan, Qijia; Zhang, Shuai; Zhang, Shanshan; Gong, Zhaojian; Shi, Lei; Liao, Qianjin; Guo, Can; Li, Yong; Li, Guiyuan; Zeng, Zhaoyang; Jiang, Weihong; Xiong, Wei; Xiang, Bo

doi:10.1186/s12943-022-01659-w

Cited by 31 publications

(13 citation statements)

References 49 publications

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“…Unlike C5, we found another subcluster, C4, derived from multiple patients and was significantly associated with worse prognosis. The functions of C4 mainly focused on pathways including EMT, Hedgehog signaling, angiogenesis, and cytoskeleton, which were usually considered being associated with tumor progression and metastasis [ 31 – 33 ]. These findings led us to focus our attention on two more specific subclusters, C4 and C7.…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13

Guo

Han

et al. 2023

J Transl Med

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Background Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer. Methods Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell–cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro. Results We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial–mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13. Conclusions Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13

Guo

Han

et al. 2023

J Transl Med

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“…CircPVT1(circBase ID: hsa_circ_0001821) locates in chromosome 8q24, and the ampli cation of circPVT1 has been frequently observed in a variety of cancers [8]. CircPVT1 regulates epithelialmesenchymal transition and tumor stemness in tumor progression, promoting tumor proliferation, invasion and metastasis [9,10]. Hua et al found that circPVT1 expression was elevated in thyroid cancer and promoted the progression of thyroid cancer [11].…”

Section: Discussionmentioning

confidence: 99%

“…CircPVT1 is located on chromosome 8q24 and plays a carcinogenic role in a variety of cancers, including lung cancer, head and neck cancer, and oral squamous cell carcinoma [5,6,7]. Several studies found circPVT1 might exert an oncogenic effect in cancer cells by stabilizing c-Myc protein expression [8,9]. It is demonstrated that circ-PVT1 regulated cellular radiosensitivity in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Li,

et al. 2023

Preprint

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Background: Circular RNA PVT1 (circPVT1) has been reported to be a vital modulator in tumorigenesis. However, the detailed regulatory mechanism of circPVT1 in breast cancer (BC) remains largely unclear. Objective: This research is to explore the mechanisms of circPVT1 in breast cancer from different perspectives. Methods: In this work, the expressions of circPVT1 and microRNA-30b-5p (miR-30b-5p) were detected by quantitative real-time PCR (qRT-PCR) in breast cancer tissues and cell lines. The Kaplan-Meierk was adopted to compare disease free survival (DFS) and overall (OS). BC cell lines MDA-MB-231and MCF-7 cell lines were chosen for the following assays. After circPVT1 was depleted, CCK-8 and Transwell assays were performed to examine the cell viability and invasive capacity. Astrocyte elevated gene 1 (AEG-1) protein level was measured by western blot. The competitive endogenous RNA molecular mechanism among circPVT1, miR-30b-5p and AEG-1 was verified by bioinformatics analysis, luciferase-reporter gene assay. Results: In the present study, it was revealed that circPVT1 expression was remarkably evaluated in BC tissues and cell lines than that in the corresponding control group. The Kaplan-Meier analysis shown that high circPVT1 expression had a significantly poorer survival prognosis than those with low circPVT1 expression in DFS (χ2 = 7.174, P = 0.007) and OS (χ2 = 3.946, P = 0.047). CircPVT1 positively regulated the proliferation, migration and invasion progression of BC cells. Besides, miR-30b-5p was identified as a target of circPVT1, and AEG-1 was identified as a target of miR-30b-5p. The depletion of circPVT1 promoted the expression of miR-30b-5p and suppressed AEG-1 expression. Moreover, simultaneous inhibition of miR-30b-5p expression in the circPVT1 knockout group could reverse the inhibition of AEG-1 expression. Conclusion: In conclusion, our results indicate circPVT1 regulates AEG-1 expression by competitively binding to endogenous miR-30b-5p in breast cancer cells. CircPVT1 promoted AEG-1 expression by negatively regulating miR-30b-5p expression to enhance the cell viability, migration, and invasion progression of BC cells. Our results reveal a new molecular therapy target for breast cancer.

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“…The production of circRNAs is regulated by a variety of factors [29][30][31] , and PAX5, a transcription factor, can promote the synthesis of various circRNAs 26 . To further explore the transcriptional regulatory mechanism of circSOD2 in ccRCC, we used the JASPAR 32 (https://jaspar.elixir.no/), HumanTFDB 33 (http://bioinfo.life.hust.edu.cn/HumanTFDB#!/), and PROMO 34 (https://alggen.lsi.upc.es/cgibin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3) databases to search for possible transcription factors that might regulate circSOD2.…”

Section: Pax5 Enhances the Biosynthesis Of Circsod2 In Ccrcc Cellsmentioning

confidence: 99%

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop

Yao,

Fu,

Dai

et al. 2024

Preprint

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Background Existing studies found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated.Methods Patient cohorts from online database were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and target gene were identified using bioinformatics and was validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing.Results CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitively bind to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor.Conclusion A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may plan an important role in the diagnosis and prognostic prediction in ccRCC patients.

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Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

Cited by 31 publications

References 49 publications

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13

Circular RNA PVT1 Promotes Breast Cancer Progression via miR-30b-5p/AEG-1 Axis

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop

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