The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway

Wang, Jiaqi; Zhang, Yi; Hu, Song; Yin, Hang; Jiang, Tao; Xu, Yixin; Liu, Lianyu; Wang, Hongyu; Gao, Hong; Wang, Renhao; Song, Jun

doi:10.1186/s12943-021-01375-x

Cited by 87 publications

(55 citation statements)

References 30 publications

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“…For example, circCAMSAP1 promotes CRC cells growth via the miR-328-5p/E2F1 axis [ 37 ]. circSPARC enhances the proliferation and migration of CRC by sponging miR-485-3p to upregulate JAK2 expression and recruiting FUS to facilitate the nuclear translocation of p-STAT3 [ 40 ]. circPPP1R12A encodes circPPP1R12A-73aa to promote colon cancer progression through activating Hippo-YAP signaling pathway [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

et al. 2021

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Background Constitutive activation of nuclear factor-κB (NF-κB) signaling plays a key role in the development and progression of colorectal carcinoma (CRC). However, the underlying mechanisms of excessive activation of NF-κB signaling remain largely unknown. Methods We used high throughput RNA sequencing to identify differentially expressed circular RNAs (circRNAs) between normal human intestinal epithelial cell lines and CRC cell lines. The identification of protein encoded by circPLCE1 was performed using LC–MS. The function of novel protein was validated in vitro and in vivo by gain or loss of function assays. Mechanistic results were concluded by immunoprecipitation analyses. Results A novel protein circPLCE1-411 encoded by circular RNA circPLCE1 was identified as a crucial player in the NF-κB activation of CRC. Mechanistically, circPLCE1-411 promoted the ubiquitin-dependent degradation of the critical NF-κB regulator RPS3 via directly binding the HSP90α/RPS3 complex to facilitate the dissociation of RPS3 from the complex, thereby reducing NF-κB nuclear translocation in CRC cells. Functionally, circPLCE1 inhibited tumor proliferation and metastasis in CRC cells, as well as patient-derived xenograft and orthotopic xenograft tumor models. Clinically, circPLCE1 was downregulated in CRC tissues and correlated with advanced clinical stages and poor survival. Conclusions circPLCE1 presents an epigenetic mechanism which disrupts NF-κB nuclear translocation and serves as a novel and promising therapeutic target and prognostic marker.

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Section: Discussionmentioning

confidence: 99%

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

et al. 2021

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“…Colorectal cancer (CRC) is a malignant disease with a high incidence worldwide. According to statistics, there are 945,000 new cases and nearly 700,000 deaths every year, making it one of the top four causes of cancer death [ 77 – 79 ]. Liu et al confirmed that METTL14 expression was upregulated in CRC tissues, and survival analysis showed that the METTL14 expression level was significantly correlated with the prognosis of CRC [ 80 ].…”

Section: Introductionmentioning

confidence: 99%

Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

et al. 2022

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RNA modification plays a crucial role in many biological functions, and its abnormal regulation is associated with the progression of cancer. Among them, N6-methyladenine (m6A) is the most abundant RNA modification. Methyltransferase-like 14 (METTL14) is the central component of the m6A methylated transferase complex, which is involved in the dynamic reversible process of m6A modification. METTL14 acts as both an oncogene and tumor suppressor gene to regulate the occurrence and development of various cancers. The abnormal m6A level induced by METTL14 is related to tumorigenesis, proliferation, metastasis, and invasion. To date, the molecular mechanism of METTL14 in various malignant tumors has not been fully studied. In this paper, we systematically summarize the latest research progress on METTL14 as a new biomarker for cancer diagnosis and its biological function in human tumors and discuss its potential clinical application. This study aims to provide new ideas for targeted therapy and improved prognoses in cancer.

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“…Accumulating evidence shows that circRNAs located in the cytoplasm can regulate biological functions by effectively sponging miRNAs to regulate the expression of their target genes [ 52 ]. Our previous study indicated that circSPARC overexpression upregulates the JAK2 expression by sponging miR-485-3p, thereby activating the JAK2/STAT3 pathway and enhancing CRC progression [ 53 ]. In the current study, we observed that circIL4R can act as a sponge to competitively bind with miR-761, as verified by RNA pull-down, dual-luciferase reporter, and FISH assays.…”

Section: Discussionmentioning

confidence: 99%

CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer

Jiang

Wang

et al. 2021

Mol Cancer

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Background Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored. Methods CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT–PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R. Results CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Conclusions Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.

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The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway

Cited by 87 publications

References 30 publications

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

A novel NF-κB regulator encoded by circPLCE1 inhibits colorectal carcinoma progression by promoting RPS3 ubiquitin-dependent degradation

Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation and metastasis in colorectal cancer

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