Exosomal circ_PTPRA inhibits tumorigenesis and promotes radiosensitivity in colorectal cancer by enriching the level of SMAD4 via competitively binding to miR-671-5p

Yang, Ying; Yang, Nengwen; Jun, Jiang

doi:10.1007/s10616-021-00506-y

Cited by 16 publications

(9 citation statements)

References 29 publications

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“…Although the functions of circRNAs remain largely unknown, the circRNA-miRNA-mRNA axis is known to regulate the development of different types of cancers ( 25 – 27 ). Exo-circRNAs may play a similar role in CRC ( 28 , 29 ). Based on this concept, we constructed and analyzed an Exo-ceRNA network, which provided a mechanistic understanding of exosome-mediated circRNA communication and elucidated the functions of Exo-circRNA in promoting CRC progression.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of the functions and clinical implications of exosome circRNAs in colorectal cancer

et al. 2022

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BackgroundExosome circRNAs (Exo-circRNAs) regulate cancer progression and intercellular crosstalk in the tumor microenvironment. However, their biological functions and potential clinical importance in colorectal cancer (CRC) remain unknown.MethodsWe used exoRBase 2.0 data to identify significant differentially expressed Exo-circRNAs (Exo-DEcircRNAs) in CRC patients and healthy individuals. The least absolute shrinkage and selector operation algorithm, support vector machine-recursive feature elimination, and multivariate Cox regression analyses were used to select candidate Exo-circRNAs and constructed a diagnostic model. Quantitative reverse transcription-polymerase chain reaction analysis was performed to confirm the expression of Exo-circRNAs in the serum samples of patients. Furthermore, we constructed an exosome circRNA-miRNA-mRNA network for CRC. Upregulated target mRNAs in the exosome competing endogenous RNA (Exo-ceRNA) network were used for functional and pathway enrichment analyses. We identified 22 immune cell types in CRC patients using CIBERSORT. Correlation analysis revealed the relationship between Exo-ceRNA networks and immune-infiltrating cells. The relationship between target mRNAs and immunotherapeutic response was also explored. Finally, using the Kaplan–Meier survival curve, a prognostic upregulated target mRNA was screened. We constructed a survival-related Exo-ceRNA subnetwork and explored the correlation between the Exo-ceRNA subnetwork and immune-infiltrating cells.ResultsThe constructed diagnostic model had a high area under the curve (AUC) value in both the training and validation sets (AUC = 0.744 and AUC = 0.741, respectively). qRT-PCR confirmed that the Exo-circRNAs were differentially expressed in CRC serum samples. We constructed Exo-ceRNA networks based on the interactions among seven upregulated Exo-DEcircRNAs, eight differentially expressed miRNAs, and twenty-two differentially expressed mRNAs in CRC. Functional enrichment analysis revealed that the upregulated target mRNAs were significantly enriched in cytoskeletal motor activity and the PI3K-Akt signaling pathway. Co-expression analysis showed a significant correlation between the Exo-ceRNA networks and immune cells. The significant correlation was observed between target mRNAs and the immunotherapeutic response. Additionally, based on the prognostic upregulated target gene (RGS2), we constructed a survival-related Exo-ceRNA subnetwork (Exosome hsa_circ_0050334-hsa_miR_182_5p-RGS2). CIBERSORT results revealed that the Exo-ceRNA subnetwork correlated with M2 macrophages (P = 4.6e-07, R = 0.31).ConclusionsOur study identified an Exo-diagnostic model, established Exo-ceRNA networks, and explored the correlation between Exo-ceRNA networks and immune cell infiltration in CRC. These findings elucidated the biological functions of Exo-circRNAs and their potential clinical implications.

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Section: Discussionmentioning

confidence: 99%

Integrated analysis of the functions and clinical implications of exosome circRNAs in colorectal cancer

et al. 2022

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“…Yang et al. found that exosomal circ_PTPRA inhibited CRC tumor growth by modulating the miR-671-5p/SMAD4 network ( 57 ). Through the miR-1305/TGF-β2/SMAD3 pathway, exosomal circCOG2 can transmit from cancer cells with high metastatic potential to cancer cells with low metastatic potential, promoting CRC proliferation, migration and invasion ( 58 ).…”

Section: Overview Of Exosomesmentioning

confidence: 99%

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

Chen

Jia

et al. 2022

Front. Oncol.

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Colorectal cancer (CRC) is the second leading cause of cancer death and the third most prevalent malignancy. Colorectal tumors exchange information with the surrounding environment and influence each other, which collectively constitutes the tumor microenvironment (TME) of CRC. Many studies have shown that exosome-derived non-coding RNAs (ncRNAs) play important roles in various pathophysiological processes by regulating the TME of CRC. This review summarizes recent findings on the fundamental roles of exosomal ncRNAs in angiogenesis, vascular permeability, tumor immunity, tumor metabolism and drug resistance. Certainly, the in-depth understanding of exosomal ncRNAs will provide comprehensive insights into the clinical application of these molecules against CRC.

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“…Taken together, circ_PTPRA inhibits growth and radioresistance of colorectal cancer cells through down-regulation of miR-671-5p levels. Moreover, suppression of miR-671-5p has also blocked growth and radioresistance of these cells through enrichment of expression of SMAD4 ( Yang et al, 2022b ). Another study in this type of cancer has shown overexpression of a circular RNA, namely circGLIS2.…”

Section: Cell Line Studiesmentioning

confidence: 99%

“…Similar results have been obtained in xenograft models of ovarian cancer ( Peng et al, 2022 ). On the other hand, studies in animal models of colorectal cancer have reported opposite results ( Yang et al, 2022b ). Detailed information about the role of miR-671 in animal models of cancer is presented in Table 2 .…”

Section: Cell Line Studiesmentioning

confidence: 99%

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A review on the role of miR-671 in human disorders

Ghafouri‐Fard

Askari

Hussen

et al. 2022

Front. Mol. Biosci.

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miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinson’s disease, rheumatoid arthritis, acute myocardial infarction and Crohn’s disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies.

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Exosomal circ_PTPRA inhibits tumorigenesis and promotes radiosensitivity in colorectal cancer by enriching the level of SMAD4 via competitively binding to miR-671-5p

Cited by 16 publications

References 29 publications

Integrated analysis of the functions and clinical implications of exosome circRNAs in colorectal cancer

Integrated analysis of the functions and clinical implications of exosome circRNAs in colorectal cancer

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

A review on the role of miR-671 in human disorders

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