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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us.
iNature bladder cancer (BC) is the most common urinary system malignant tumor.
For patients with advanced or chemotherapy-refractory bladder cancer, although surgical techniques and drug treatment have improved, the prognosis is still poor.
The development of bladder cancer is a complex process.
Epigenetic abnormalities have been shown to play a key role in the pathogenesis of bladder cancer, including DNA and histone modification, chromatin remodeling, RNA methylation, etc.
In particular, N6-methyladenosine (m6A) is the most common RNA methylation, and it is acting as a key regulator in a variety of basic biological processes.
However, the understanding of the regulatory role and potential mechanism of m6A in bladder cancer is still limited.
It has been found that circular RNA (circRNA) has a significant impact on the progression of bladder cancer (BC) through various mechanisms.
On April 14, 2021, Huazhong University of Science and Technology Jiang Guosong and Zhang Xiaoping jointly published an online report entitled "CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression" in Molecular Cancer (IF=15.
30) Research paper, this study aims to identify a new type of circRNA that can regulate the function of IGF2BP1 (the key m6A reader), and to explore the regulatory mechanism and clinical significance of bladder cancer.The study found that IGF2BP1 mainly binds to circPTPRA in the cytoplasm of bladder cancer cells.
The ectopic expression of circPTPRA eliminated the proliferation, migration and invasion of bladder cancer cells induced by IGF2BP1.
Importantly, circPTPRA down-regulated the expression of MYC and FSCN1 by interacting with IGF2BP1.
In addition, the recognition of m6A-modified RNA mediated by IGF2BP1 was partially interfered by the interaction of circPTPRA with the KH domain of IGF2BP1.
In conclusion, this study determined that exon circular circPTPRA is a new type of tumor suppressor, which inhibits the progression of cancer by endogenously blocking IGF2BP1's recognition of m6A-modified RNA, indicating that circPTPRA can be used as a therapeutic effect for patients with bladder cancer.
Utilize therapeutic targets.
Bladder cancer (BC) is the most common urinary system malignancy, with an estimated 81,400 new cases in the United States in 2019.
For patients with advanced or chemotherapy-refractory bladder cancer, although surgical techniques and drug treatment have improved, the prognosis is still poor.
The development of bladder cancer is a complex process.
Epigenetic abnormalities have been shown to play a key role in the pathogenesis of bladder cancer, including DNA and histone modification, chromatin remodeling, RNA methylation, etc.
In particular, N6-methyladenosine (m6A) is the most common RNA methylation, and it is acting as a key regulator in a variety of basic biological processes.
However, the understanding of the regulatory role and potential mechanism of m6A in bladder cancer is still limited.
Circular RNA (circRNA) is a new type of single-stranded RNA characterized by covalently closed continuous loops and resistance to RNase R digestion.
More and more RNA sequencing analyses have revealed the evolutionary conservation and richness of circular RNA, indicating the specific role of circRNA in cell physiology.
Specifically, circRNA has been proven to be a "microRNA (miRNA) sponge", which has multiple miRNAs and functions as miRNA inhibitors.
However, genome-wide studies have shown that the sponging activity of miRNAs cannot be universally applied, and other mechanisms have been proposed, such as serving as a platform for protein interaction.
More and more evidences show that circRNA is often inactivated in various human cancers and participates in a variety of biological processes.
However, the role and mechanism of circRNA in recognizing m6A methylation is not very clear.
Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) belongs to the conserved family of RNA-bound carcinoembryonic proteins (IGF2BP1-3).
Recent studies have shown that IGF2BP1 has the most conservative "carcinogenic effect" in the IGF2BP family in tumor-derived cells by affecting the stability, translatability or localization of RNA.
Cross-linked immunoprecipitation (CLIP) analysis showed that IGF2BPs preferentially recognize m6A-modified mRNA and promote the stability and translation of potential mRNA targets in an m6A-dependent manner, thus affecting gene expression output.
However, there is still little understanding of IGF2BP1 involved in the development of bladder cancer and how it is regulated by circular RNA.
In this study, the carcinogenic role of IGF2BP1 in the process of bladder cancer was revealed, and many novel circular RNAs that interact with IGF2BP1 were identified through high-throughput sequencing.
The circRNA derived from PTPRA pre-mRNA (circPTPRA) was screened out.
The results show that circPTPRA can inhibit the growth and invasiveness of bladder cancer cells by competitively binding to the KH domain of IGF2BP1 and blocking its interaction with downstream targets m6A-modified mRNA (MYC and FSCN1).
The results of this study delineate a new mechanism of circRNA/IGF2BP1 mediated regulation of tumor progression and provide opportunities for therapeutic intervention in bladder cancer.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01359-x
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, and interested parties.
Long press or scan the QR code below to follow us.
iNature bladder cancer (BC) is the most common urinary system malignant tumor.
For patients with advanced or chemotherapy-refractory bladder cancer, although surgical techniques and drug treatment have improved, the prognosis is still poor.
The development of bladder cancer is a complex process.
Epigenetic abnormalities have been shown to play a key role in the pathogenesis of bladder cancer, including DNA and histone modification, chromatin remodeling, RNA methylation, etc.
In particular, N6-methyladenosine (m6A) is the most common RNA methylation, and it is acting as a key regulator in a variety of basic biological processes.
However, the understanding of the regulatory role and potential mechanism of m6A in bladder cancer is still limited.
It has been found that circular RNA (circRNA) has a significant impact on the progression of bladder cancer (BC) through various mechanisms.
On April 14, 2021, Huazhong University of Science and Technology Jiang Guosong and Zhang Xiaoping jointly published an online report entitled "CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression" in Molecular Cancer (IF=15.
30) Research paper, this study aims to identify a new type of circRNA that can regulate the function of IGF2BP1 (the key m6A reader), and to explore the regulatory mechanism and clinical significance of bladder cancer.The study found that IGF2BP1 mainly binds to circPTPRA in the cytoplasm of bladder cancer cells.
The ectopic expression of circPTPRA eliminated the proliferation, migration and invasion of bladder cancer cells induced by IGF2BP1.
Importantly, circPTPRA down-regulated the expression of MYC and FSCN1 by interacting with IGF2BP1.
In addition, the recognition of m6A-modified RNA mediated by IGF2BP1 was partially interfered by the interaction of circPTPRA with the KH domain of IGF2BP1.
In conclusion, this study determined that exon circular circPTPRA is a new type of tumor suppressor, which inhibits the progression of cancer by endogenously blocking IGF2BP1's recognition of m6A-modified RNA, indicating that circPTPRA can be used as a therapeutic effect for patients with bladder cancer.
Utilize therapeutic targets.
Bladder cancer (BC) is the most common urinary system malignancy, with an estimated 81,400 new cases in the United States in 2019.
For patients with advanced or chemotherapy-refractory bladder cancer, although surgical techniques and drug treatment have improved, the prognosis is still poor.
The development of bladder cancer is a complex process.
Epigenetic abnormalities have been shown to play a key role in the pathogenesis of bladder cancer, including DNA and histone modification, chromatin remodeling, RNA methylation, etc.
In particular, N6-methyladenosine (m6A) is the most common RNA methylation, and it is acting as a key regulator in a variety of basic biological processes.
However, the understanding of the regulatory role and potential mechanism of m6A in bladder cancer is still limited.
Circular RNA (circRNA) is a new type of single-stranded RNA characterized by covalently closed continuous loops and resistance to RNase R digestion.
More and more RNA sequencing analyses have revealed the evolutionary conservation and richness of circular RNA, indicating the specific role of circRNA in cell physiology.
Specifically, circRNA has been proven to be a "microRNA (miRNA) sponge", which has multiple miRNAs and functions as miRNA inhibitors.
However, genome-wide studies have shown that the sponging activity of miRNAs cannot be universally applied, and other mechanisms have been proposed, such as serving as a platform for protein interaction.
More and more evidences show that circRNA is often inactivated in various human cancers and participates in a variety of biological processes.
However, the role and mechanism of circRNA in recognizing m6A methylation is not very clear.
Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) belongs to the conserved family of RNA-bound carcinoembryonic proteins (IGF2BP1-3).
Recent studies have shown that IGF2BP1 has the most conservative "carcinogenic effect" in the IGF2BP family in tumor-derived cells by affecting the stability, translatability or localization of RNA.
Cross-linked immunoprecipitation (CLIP) analysis showed that IGF2BPs preferentially recognize m6A-modified mRNA and promote the stability and translation of potential mRNA targets in an m6A-dependent manner, thus affecting gene expression output.
However, there is still little understanding of IGF2BP1 involved in the development of bladder cancer and how it is regulated by circular RNA.
In this study, the carcinogenic role of IGF2BP1 in the process of bladder cancer was revealed, and many novel circular RNAs that interact with IGF2BP1 were identified through high-throughput sequencing.
The circRNA derived from PTPRA pre-mRNA (circPTPRA) was screened out.
The results show that circPTPRA can inhibit the growth and invasiveness of bladder cancer cells by competitively binding to the KH domain of IGF2BP1 and blocking its interaction with downstream targets m6A-modified mRNA (MYC and FSCN1).
The results of this study delineate a new mechanism of circRNA/IGF2BP1 mediated regulation of tumor progression and provide opportunities for therapeutic intervention in bladder cancer.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01359-x
