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Editor’s note iNature is China’s largest academic public account.
It is jointly created by a team of doctors from Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature talent public account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
More and more iNature studies have shown that the abnormal expression of circular RNA (circRNA) is widely involved in the occurrence and progression of malignant tumors including colorectal cancer (CRC)
.
However, the clinical significance, level, characteristics, biological function and molecular mechanism of new circRNA in CRC remain to be explored to a large extent
.
On December 18, 2021, Song Jun and Wang Renhao from Xuzhou Medical University published an online communication titled “CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation in Molecular Cancer (IF=27).
and metastasis in colorectal cancer" research paper, based on bioinformatics analysis, this study identified a new CRC-related circRNA (hsa_circ_0038718), which is derived from exons 3 and 4 of the IL4R gene, also known as circIL4R
.
The study found that CircIL4R was up-regulated in CRC cell lines and the serum and tissues of CRC patients, and was positively correlated with advanced clinicopathological characteristics and poor prognosis
.
Functional experiments show that circIL4R promotes the proliferation, migration and invasion of CRC cells through the PI3K/AKT signaling pathway
.
In terms of mechanism, circIL4R is regulated by TFAP2C and competitively interacts with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway, thereby promoting the progression of CRC
.
In summary, the results of this study indicate that the up-regulation of circIL4R plays a carcinogenic role in the progression of CRC, and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment
.
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system and the second leading cause of cancer-related deaths in the world
.
The National Comprehensive Cancer Network (NCCN) guidelines recommend surgery combined with radiotherapy and chemotherapy as the standard treatment for CRC
.
Although the treatment of colorectal cancer has improved, unfortunately the prognosis of colorectal cancer is still unsatisfactory, mainly because the tumorigenesis mechanism of colorectal cancer is unclear and aggressive; about 880,000 CRC patients die every year
.
Therefore, it is urgent to understand and explore the potential mechanism of CRC's malignant progression in order to improve the diagnosis efficiency, treatment effect and prognosis
.
Circular RNA (circRNA) is a new type of bifunctional RNA with non-coding and limited protein coding functions.
It is produced by the non-classical reverse splicing junction of the precursor mRNA and is characterized by a covalently closed single-stranded loop structure.
.
Due to the lack of a 5'cap and 3'poly A tail, circRNAs are resistant to exonuclease and are more stable than their linear RNA counterparts
.
In addition, with the development of high-throughput sequencing combined with existing bioinformatics analysis technology, more and more evidences show that circRNA is widely expressed in malignant cancers including CRC, is generally stable, highly conservative, and tissue or cell specific
.
For example, it is reported that circRNA ciRS-7-A, circNSUN2 and circ-ERBIN are overexpressed in CRC and promote its progression
.
circRNA can perform its biological functions by acting as a microRNA (miRNA) sponge and interacting with RNA binding protein (RBP)
.
In addition, some circRNAs can be used as protein translation templates or scaffolds or regulators of RNA splicing and gene transcription
.
Abnormally expressed circRNA also plays an important role in mediating cancer progression by regulating the activity of a variety of signaling pathways, such as WNT/β-catenin, MAPK, JAK/STAT, NOTCH and PI3K/AKT pathways
.
According to reports, circPPP1R12A promotes the onset and metastasis of colon cancer through the Hippo-YAP signaling pathway
.
In summary, circRNA can be used as a potential biomarker for the diagnosis and prognosis of CRC, as well as an effective therapeutic target and an important regulator of signaling pathways
.
TRIM29 (also known as ATDC) is a member of the tripartite motif protein family and has been shown to play a carcinogenic role in various cancers, including pancreatic cancer, thyroid cancer, bladder cancer and CRC
.
More and more studies have confirmed that circRNAs play a role in the occurrence and progression of a variety of malignant tumors by regulating target genes
.
Therefore, studying the relationship between circRNAs and TRIM29 is of great significance for exploring the upstream regulation of TRIM29 and developing promising CRC therapeutic targets
.
Article pattern (picture from Molecular Cancer) In recent years, the abnormal expression and regulation axis of circRNA have been clarified and described in a variety of malignant tumors
.
However, only preliminary studies have been conducted on the role of circRNAs in CRC, and the clinical significance, level, biological function and molecular mechanism of new circRNAs in CRC are still to be explored to a large extent
.
In this study, based on bioinformatics analysis, a new CRC-related circRNA (hsa_circ_0038718) was identified, which is derived from exons 3 and 4 of the IL4R gene, also known as circIL4R
.
The expression and function of circIL4R in CRC are unclear
.
Therefore, first perform in situ hybridization (ISH) and qRT-PCR to determine the level of circIL4R and the clinical significance of its expression
.
Subsequently, in vitro and in vivo function gain and loss experiments were performed to identify the biological function and molecular mechanism of circIL4R in CRC
.
More precisely, a series of experiments, such as chromatin immunoprecipitation (ChIP), luciferase reporter gene, and biotinylated RNA pull-down assay, show that circIL4R induced by TFAP2C can act as a sponge for miR-761 to enhance TRIM29 expression and force Overexpression of TRIM29 promotes ubiquitin-mediated degradation of PHLPP1, activates the PI3K/AKT signaling pathway, and promotes the proliferation and metastasis of CRC cells
.
Overall, the results of the study indicate that circIL4R can be used as a new diagnostic and prognostic biomarker and a promising target for CRC treatment
.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01474-9
It is jointly created by a team of doctors from Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature talent public account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
More and more iNature studies have shown that the abnormal expression of circular RNA (circRNA) is widely involved in the occurrence and progression of malignant tumors including colorectal cancer (CRC)
.
However, the clinical significance, level, characteristics, biological function and molecular mechanism of new circRNA in CRC remain to be explored to a large extent
.
On December 18, 2021, Song Jun and Wang Renhao from Xuzhou Medical University published an online communication titled “CircIL4R activates the PI3K/AKT signaling pathway via the miR-761/TRIM29/PHLPP1 axis and promotes proliferation in Molecular Cancer (IF=27).
and metastasis in colorectal cancer" research paper, based on bioinformatics analysis, this study identified a new CRC-related circRNA (hsa_circ_0038718), which is derived from exons 3 and 4 of the IL4R gene, also known as circIL4R
.
The study found that CircIL4R was up-regulated in CRC cell lines and the serum and tissues of CRC patients, and was positively correlated with advanced clinicopathological characteristics and poor prognosis
.
Functional experiments show that circIL4R promotes the proliferation, migration and invasion of CRC cells through the PI3K/AKT signaling pathway
.
In terms of mechanism, circIL4R is regulated by TFAP2C and competitively interacts with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway, thereby promoting the progression of CRC
.
In summary, the results of this study indicate that the up-regulation of circIL4R plays a carcinogenic role in the progression of CRC, and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment
.
Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system and the second leading cause of cancer-related deaths in the world
.
The National Comprehensive Cancer Network (NCCN) guidelines recommend surgery combined with radiotherapy and chemotherapy as the standard treatment for CRC
.
Although the treatment of colorectal cancer has improved, unfortunately the prognosis of colorectal cancer is still unsatisfactory, mainly because the tumorigenesis mechanism of colorectal cancer is unclear and aggressive; about 880,000 CRC patients die every year
.
Therefore, it is urgent to understand and explore the potential mechanism of CRC's malignant progression in order to improve the diagnosis efficiency, treatment effect and prognosis
.
Circular RNA (circRNA) is a new type of bifunctional RNA with non-coding and limited protein coding functions.
It is produced by the non-classical reverse splicing junction of the precursor mRNA and is characterized by a covalently closed single-stranded loop structure.
.
Due to the lack of a 5'cap and 3'poly A tail, circRNAs are resistant to exonuclease and are more stable than their linear RNA counterparts
.
In addition, with the development of high-throughput sequencing combined with existing bioinformatics analysis technology, more and more evidences show that circRNA is widely expressed in malignant cancers including CRC, is generally stable, highly conservative, and tissue or cell specific
.
For example, it is reported that circRNA ciRS-7-A, circNSUN2 and circ-ERBIN are overexpressed in CRC and promote its progression
.
circRNA can perform its biological functions by acting as a microRNA (miRNA) sponge and interacting with RNA binding protein (RBP)
.
In addition, some circRNAs can be used as protein translation templates or scaffolds or regulators of RNA splicing and gene transcription
.
Abnormally expressed circRNA also plays an important role in mediating cancer progression by regulating the activity of a variety of signaling pathways, such as WNT/β-catenin, MAPK, JAK/STAT, NOTCH and PI3K/AKT pathways
.
According to reports, circPPP1R12A promotes the onset and metastasis of colon cancer through the Hippo-YAP signaling pathway
.
In summary, circRNA can be used as a potential biomarker for the diagnosis and prognosis of CRC, as well as an effective therapeutic target and an important regulator of signaling pathways
.
TRIM29 (also known as ATDC) is a member of the tripartite motif protein family and has been shown to play a carcinogenic role in various cancers, including pancreatic cancer, thyroid cancer, bladder cancer and CRC
.
More and more studies have confirmed that circRNAs play a role in the occurrence and progression of a variety of malignant tumors by regulating target genes
.
Therefore, studying the relationship between circRNAs and TRIM29 is of great significance for exploring the upstream regulation of TRIM29 and developing promising CRC therapeutic targets
.
Article pattern (picture from Molecular Cancer) In recent years, the abnormal expression and regulation axis of circRNA have been clarified and described in a variety of malignant tumors
.
However, only preliminary studies have been conducted on the role of circRNAs in CRC, and the clinical significance, level, biological function and molecular mechanism of new circRNAs in CRC are still to be explored to a large extent
.
In this study, based on bioinformatics analysis, a new CRC-related circRNA (hsa_circ_0038718) was identified, which is derived from exons 3 and 4 of the IL4R gene, also known as circIL4R
.
The expression and function of circIL4R in CRC are unclear
.
Therefore, first perform in situ hybridization (ISH) and qRT-PCR to determine the level of circIL4R and the clinical significance of its expression
.
Subsequently, in vitro and in vivo function gain and loss experiments were performed to identify the biological function and molecular mechanism of circIL4R in CRC
.
More precisely, a series of experiments, such as chromatin immunoprecipitation (ChIP), luciferase reporter gene, and biotinylated RNA pull-down assay, show that circIL4R induced by TFAP2C can act as a sponge for miR-761 to enhance TRIM29 expression and force Overexpression of TRIM29 promotes ubiquitin-mediated degradation of PHLPP1, activates the PI3K/AKT signaling pathway, and promotes the proliferation and metastasis of CRC cells
.
Overall, the results of the study indicate that circIL4R can be used as a new diagnostic and prognostic biomarker and a promising target for CRC treatment
.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01474-9
