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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, interested parties can Long press or scan the QR code below to follow us.
Non-coding RNAs such as iNature circular RNA (circRNA) are abundant in the human body and affect the occurrence and development of various diseases.
However, the biological function of circRNAs in colorectal cancer (CRC) is largely unknown.
On June 1, 2021, Song Jun and Wang Renhao from Xuzhou Medical University published an online report entitled "The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway" in Molecular Cancer (IF=15.
30) Research paper, the study found that CircSPARC was up-regulated in the tissues and plasma of CRC patients.
The high expression of circSPARC is associated with advanced TNM staging, lymph node metastasis and poor survival.
Silencing circSPARC inhibits CRC cell migration and proliferation in vitro and in vivo.
In terms of mechanism, circSPARC absorbs miR-485-3p to up-regulate JAK2 expression and ultimately promotes the accumulation of phosphorylated (p)-STAT3.
In addition, circSPARC recruited FUS, which promoted the nuclear translocation of p-STAT3.
In summary, these findings indicate that circSPARC may regulate the JAK2/STAT3 pathway as a potential diagnostic and prognostic biomarker as well as a therapeutic target for CRC treatment.
Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality in the world.
In addition to genetics, obesity, lack of exercise, poor diet, drinking, and smoking are all factors that contribute to the development of CRC.
In addition, the rising incidence of CRC tends to shift to developing countries and younger age groups.
At present, with the development of technologies such as cancer biomarkers, colonoscopy, laparoscopic surgery, and radiotherapy and chemotherapy, treatment options for CRC patients have increased.
However, post-treatment problems including recurrence, metastasis, and chemoresistance are related to poor prognosis and need to be addressed.
It has been reported that the progress of CRC is closely related to the disorder of genes and signal pathways.
Therefore, in order to achieve early diagnosis and better prognosis, new biomarkers and therapeutic targets for colorectal cancer should be studied.
Circular RNA (circRNA) was first discovered more than 40 years ago.
It is a type of endogenous non-coding RNA (ncRNA) with a closed-loop structure, lacking a 5'end cap and a 3'end poly(A) tail.
A recent study showed that circRNA may not have a simple circular structure, but may contain double-stranded internal complementary base pairing sequences (ICBPS), which has been explored in many circRNAs.
Due to their unique structure, circRNAs are more stable than mRNAs, more resistant to degradation, and cannot be amplified in genomic DNA.
The development of high-throughput RNA sequencing and the application of bioinformatics technology have confirmed that circRNA is an important molecule that can be abnormally expressed and is related to the poor prognosis and chemoresistance of cancer.
According to recent studies, circRNA mainly acts as microRNA (miRNA) sponges through the presence of miRNA response elements (MRE), specific sequence motifs complementary to specific miRNAs, and acts as competitive endogenous RNA (ceRNA) to mitigate miRNA-mediated inhibition Downstream target mRNA.
Similar to their role as miRNA sponges, some circRNAs have RNA binding protein (RBP) binding sites that can recruit or inhibit RBP.
In addition, some studies have found that some circRNAs have transcriptional and post-transcriptional regulatory functions, while others can even be translated into proteins.
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in cancer cell migration, growth and differentiation.
When activated by cytokines, JAK will activate signaling molecules, such as STAT.
The activated STATs transfer from the cytoplasm to the nucleus, where they enhance the transcription of target genes.
The most important molecules in this signaling pathway are JAK2 and STAT3.
After being activated by cytokines, several JAK2 molecules approach each other and autophosphorylate to form phosphorylated (p)-JAK2.
Then, p-JAK2 activates STAT3 through phosphorylation, and the translocation of p-STAT3 into the nucleus leads to enhanced transcription of several genes, such as epithelial-mesenchymal transition (EMT)-related genes, c-myc, MMP2, and p53.
In CRC, the JAK/STAT signaling pathway can enhance the invasion, migration, growth and chemoresistance of cancer cells, and regulate cell progression, apoptosis and cell cycle progression.
In this study, RNA-seq was used to analyze the expression of circRNA in CRC tissues.
The expression level of hsa_circ_0004104 in colorectal cancer tissues is significantly up-regulated, which is closely related to the prognosis of colorectal cancer patients.
In addition, the up-regulation of hsa_circ_0004104 promotes cell proliferation and migration.
Hsa_circ_0004104 shows that it is the sponges of miR-485-3p, which can degrade JAK2 mRNA.
In addition, hsa_circ_0004104 can bind to FUS, which is an RBP that has been identified to promote the translocation of p-STAT3 into the nucleus.
In short, hsa_circ_0004104 regulates the JAK2/STAT3 pathway by acting as a ceRNA to bind to miR-485-3p and FUS.
Hsa_circ_0004104 can be used as a new biomarker for the diagnosis and prognosis of colorectal cancer, and may become a potential therapeutic target for patients with colorectal cancer.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01375-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, interested parties can Long press or scan the QR code below to follow us.
Non-coding RNAs such as iNature circular RNA (circRNA) are abundant in the human body and affect the occurrence and development of various diseases.
However, the biological function of circRNAs in colorectal cancer (CRC) is largely unknown.
On June 1, 2021, Song Jun and Wang Renhao from Xuzhou Medical University published an online report entitled "The circular RNA circSPARC enhances the migration and proliferation of colorectal cancer by regulating the JAK/STAT pathway" in Molecular Cancer (IF=15.
30) Research paper, the study found that CircSPARC was up-regulated in the tissues and plasma of CRC patients.
The high expression of circSPARC is associated with advanced TNM staging, lymph node metastasis and poor survival.
Silencing circSPARC inhibits CRC cell migration and proliferation in vitro and in vivo.
In terms of mechanism, circSPARC absorbs miR-485-3p to up-regulate JAK2 expression and ultimately promotes the accumulation of phosphorylated (p)-STAT3.
In addition, circSPARC recruited FUS, which promoted the nuclear translocation of p-STAT3.
In summary, these findings indicate that circSPARC may regulate the JAK2/STAT3 pathway as a potential diagnostic and prognostic biomarker as well as a therapeutic target for CRC treatment.
Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality in the world.
In addition to genetics, obesity, lack of exercise, poor diet, drinking, and smoking are all factors that contribute to the development of CRC.
In addition, the rising incidence of CRC tends to shift to developing countries and younger age groups.
At present, with the development of technologies such as cancer biomarkers, colonoscopy, laparoscopic surgery, and radiotherapy and chemotherapy, treatment options for CRC patients have increased.
However, post-treatment problems including recurrence, metastasis, and chemoresistance are related to poor prognosis and need to be addressed.
It has been reported that the progress of CRC is closely related to the disorder of genes and signal pathways.
Therefore, in order to achieve early diagnosis and better prognosis, new biomarkers and therapeutic targets for colorectal cancer should be studied.
Circular RNA (circRNA) was first discovered more than 40 years ago.
It is a type of endogenous non-coding RNA (ncRNA) with a closed-loop structure, lacking a 5'end cap and a 3'end poly(A) tail.
A recent study showed that circRNA may not have a simple circular structure, but may contain double-stranded internal complementary base pairing sequences (ICBPS), which has been explored in many circRNAs.
Due to their unique structure, circRNAs are more stable than mRNAs, more resistant to degradation, and cannot be amplified in genomic DNA.
The development of high-throughput RNA sequencing and the application of bioinformatics technology have confirmed that circRNA is an important molecule that can be abnormally expressed and is related to the poor prognosis and chemoresistance of cancer.
According to recent studies, circRNA mainly acts as microRNA (miRNA) sponges through the presence of miRNA response elements (MRE), specific sequence motifs complementary to specific miRNAs, and acts as competitive endogenous RNA (ceRNA) to mitigate miRNA-mediated inhibition Downstream target mRNA.
Similar to their role as miRNA sponges, some circRNAs have RNA binding protein (RBP) binding sites that can recruit or inhibit RBP.
In addition, some studies have found that some circRNAs have transcriptional and post-transcriptional regulatory functions, while others can even be translated into proteins.
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is involved in cancer cell migration, growth and differentiation.
When activated by cytokines, JAK will activate signaling molecules, such as STAT.
The activated STATs transfer from the cytoplasm to the nucleus, where they enhance the transcription of target genes.
The most important molecules in this signaling pathway are JAK2 and STAT3.
After being activated by cytokines, several JAK2 molecules approach each other and autophosphorylate to form phosphorylated (p)-JAK2.
Then, p-JAK2 activates STAT3 through phosphorylation, and the translocation of p-STAT3 into the nucleus leads to enhanced transcription of several genes, such as epithelial-mesenchymal transition (EMT)-related genes, c-myc, MMP2, and p53.
In CRC, the JAK/STAT signaling pathway can enhance the invasion, migration, growth and chemoresistance of cancer cells, and regulate cell progression, apoptosis and cell cycle progression.
In this study, RNA-seq was used to analyze the expression of circRNA in CRC tissues.
The expression level of hsa_circ_0004104 in colorectal cancer tissues is significantly up-regulated, which is closely related to the prognosis of colorectal cancer patients.
In addition, the up-regulation of hsa_circ_0004104 promotes cell proliferation and migration.
Hsa_circ_0004104 shows that it is the sponges of miR-485-3p, which can degrade JAK2 mRNA.
In addition, hsa_circ_0004104 can bind to FUS, which is an RBP that has been identified to promote the translocation of p-STAT3 into the nucleus.
In short, hsa_circ_0004104 regulates the JAK2/STAT3 pathway by acting as a ceRNA to bind to miR-485-3p and FUS.
Hsa_circ_0004104 can be used as a new biomarker for the diagnosis and prognosis of colorectal cancer, and may become a potential therapeutic target for patients with colorectal cancer.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01375-x
