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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.
iNature liver cirrhosis is a recognized risk factor for the development of hepatocellular carcinoma (HCC).
Few studies have reported the expression of circRNA in HCC samples compared with samples from adjacent abnormal hyperplastic nodules (DN).
On May 13, 2021, Fudan University Fan Jia and Shi Guoming jointly published a study titled "CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity" in Molecular Cancer (IF=15.
30).
The paper, the study found that circMEMO1 was significantly down-regulated in HCC samples, and the level of circMEMO1 was closely related to the OS and disease-free survival (DFS) of HCC patients.
Mechanism analysis shows that circMEMO1 can regulate the promoter methylation and gene expression of TCF21 by acting as a sponge for miR-106b-5p, thereby regulating the HCC process, while miR-106b-5p targets the TET gene family and increases the level of 5hmC .
More importantly, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment.
In conclusion, this study determined that circMEMO1 can promote the demethylation and expression of TCF21, and it can be considered as a crucial epigenetic modifier in the process of HCC.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and the third most common cause of cancer-related deaths.
Even after surgery, the overall prognosis of HCC patients is still unsatisfactory.
Metastasis remains the most challenging problem affecting the prognosis of HCC patients.
Despite recent significant progress in molecular targeted therapy and immunotherapy for HCC, sorafenib is still the first-line treatment standard for many patients with advanced HCC (including patients with locally advanced HCC).
Identifying key drug candidates that regulate the metastasis of liver cancer and the sensitivity to sorafenib therapy may help improve the prognosis and therapeutic effect of patients.
The development of liver cancer has been described as a multi-step process, from dysplastic nodules (DNs) to liver cancer foci, followed by small liver cancer, and finally obvious cancer.
Circular RNA (circRNA) is a new type of endogenous non-coding RNA that forms a covalent closed loop, which plays a vital role in tumorigenesis and tumor progression.
Few studies have reported the expression of circRNA in HCC samples compared with adjacent DN samples.
Transcription factor 21 (TCF21), a member of the class II bHLH transcription factor superfamily, has been shown to be abnormally methylated and often silenced in human malignancies.
TCF21 not only mediates cell fate and differentiation by coordinating the spatiotemporal gene expression during the development of various organs, but also is considered to participate in a wide range of important biological processes (such as cell proliferation, differentiation, survival, cell cycle, invasion and metastasis) The key regulator.
Due to its key role in transcriptional regulation, TCF21 has great potential as an effective therapeutic target for many cancers.
However, the regulatory mechanism, including the reason for the abnormal regulation of TCF21 in liver cancer tissue, remains unresolved.
Here, the study used the Arraystar Human circRNA array combined with laser capture microdissection (LCM) to identify the significant down-regulation of circMEMO1 in HCC tissue samples.
The level of circMEMO1 in liver cancer tissue is closely related to the prognosis of liver cancer patients.
Mechanism analysis shows that circMEMO1 can act as a sponge of miR-106b-5p, thereby promoting the demethylation process of the TCF21 promoter, and then further activate the transcription and expression of TCF21, which targets TET family genes and increases 5hmC levels.
In addition, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment.
Therefore, circMEMO1 can be considered as a key epigenetic modifier that regulates the progression of HCC.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01361-3
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.
iNature liver cirrhosis is a recognized risk factor for the development of hepatocellular carcinoma (HCC).
Few studies have reported the expression of circRNA in HCC samples compared with samples from adjacent abnormal hyperplastic nodules (DN).
On May 13, 2021, Fudan University Fan Jia and Shi Guoming jointly published a study titled "CircMEMO1 modulates the promoter methylation and expression of TCF21 to regulate hepatocellular carcinoma progression and sorafenib treatment sensitivity" in Molecular Cancer (IF=15.
30).
The paper, the study found that circMEMO1 was significantly down-regulated in HCC samples, and the level of circMEMO1 was closely related to the OS and disease-free survival (DFS) of HCC patients.
Mechanism analysis shows that circMEMO1 can regulate the promoter methylation and gene expression of TCF21 by acting as a sponge for miR-106b-5p, thereby regulating the HCC process, while miR-106b-5p targets the TET gene family and increases the level of 5hmC .
More importantly, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment.
In conclusion, this study determined that circMEMO1 can promote the demethylation and expression of TCF21, and it can be considered as a crucial epigenetic modifier in the process of HCC.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and the third most common cause of cancer-related deaths.
Even after surgery, the overall prognosis of HCC patients is still unsatisfactory.
Metastasis remains the most challenging problem affecting the prognosis of HCC patients.
Despite recent significant progress in molecular targeted therapy and immunotherapy for HCC, sorafenib is still the first-line treatment standard for many patients with advanced HCC (including patients with locally advanced HCC).
Identifying key drug candidates that regulate the metastasis of liver cancer and the sensitivity to sorafenib therapy may help improve the prognosis and therapeutic effect of patients.
The development of liver cancer has been described as a multi-step process, from dysplastic nodules (DNs) to liver cancer foci, followed by small liver cancer, and finally obvious cancer.
Circular RNA (circRNA) is a new type of endogenous non-coding RNA that forms a covalent closed loop, which plays a vital role in tumorigenesis and tumor progression.
Few studies have reported the expression of circRNA in HCC samples compared with adjacent DN samples.
Transcription factor 21 (TCF21), a member of the class II bHLH transcription factor superfamily, has been shown to be abnormally methylated and often silenced in human malignancies.
TCF21 not only mediates cell fate and differentiation by coordinating the spatiotemporal gene expression during the development of various organs, but also is considered to participate in a wide range of important biological processes (such as cell proliferation, differentiation, survival, cell cycle, invasion and metastasis) The key regulator.
Due to its key role in transcriptional regulation, TCF21 has great potential as an effective therapeutic target for many cancers.
However, the regulatory mechanism, including the reason for the abnormal regulation of TCF21 in liver cancer tissue, remains unresolved.
Here, the study used the Arraystar Human circRNA array combined with laser capture microdissection (LCM) to identify the significant down-regulation of circMEMO1 in HCC tissue samples.
The level of circMEMO1 in liver cancer tissue is closely related to the prognosis of liver cancer patients.
Mechanism analysis shows that circMEMO1 can act as a sponge of miR-106b-5p, thereby promoting the demethylation process of the TCF21 promoter, and then further activate the transcription and expression of TCF21, which targets TET family genes and increases 5hmC levels.
In addition, circMEMO1 can increase the sensitivity of HCC cells to sorafenib treatment.
Therefore, circMEMO1 can be considered as a key epigenetic modifier that regulates the progression of HCC.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01361-3
