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iNaturePTEN is one of the most frequently mutated genes in human cancers
.
Although the roles of canonical PTEN proteins and PTEN isoforms have been extensively explored, the current understanding of PTEN family members does not fully account for the diversity of their roles in biological processes and tumor development
.
Notably, the function of the noncoding RNAs produced by PTEN is unknown
.
On February 8, 2022, a research paper entitled "circPTEN1, a circular RNA generated from PTEN, suppresses cancer progression through inhibition of TGF-β/Smad signaling" was published online by Peking University Yin Yuxin's team in Molecular Cancer (IF=27).
The study identified a circular RNA produced by the PTEN gene, called circPTEN1, that is frequently downregulated in colorectal cancer, and that reduced expression of circPTEN1 predicts poorer survival
.
Low expression of circPTEN1 promoted metastasis in PDX models in vivo and accelerated cancer cell invasion in vitro, whereas overexpression of circPTEN1 exhibited the opposite effect
.
Mechanistically, this study found that circPTEN1 was able to bind the MH2 domain of Smad4 to disrupt its physical interaction with Smad2/3, thereby reducing Smad complex formation and subsequent nuclear translocation, and thus inhibited upon TGF-β stimulation Its expression of downstream genes associated with epithelial-mesenchymal transition
.
Furthermore, this study found that eIF4A3 inhibits the cyclization of circPTEN1 by directly binding to the flanking regions of circPTEN1
.
In conclusion, this study revealed a circRNA with tumor suppressor function produced by a novel PTEN gene, and further revealed the mechanism of circPTEN1 in TGF-β-mediated CRC metastasis
.
The identification of circPTEN1 provides a new direction for PTEN research, and elucidation of circPTEN1/TGF-β/Smad signaling may pave the way for the development of potential therapeutic strategies to inhibit cancer progression
.
In addition, on February 2, 2022, Yuxin Yin and Jun Wang of Peking University jointly published a study titled "Lung cancer scRNA-seq and lipidomics reveal aberrant lipid metabolism for early-stage diagnosis" in Science Translational Medicine (IF=17.
96).
In the paper, the study performed single-cell RNA sequencing of different early-stage lung cancers and found that lipid metabolism was widely dysregulated in different cell types, with glycerophospholipid metabolism being the most altered lipid metabolism-related pathway
.
Untargeted lipidomics was performed in an exploratory cohort of 311 participants
.
Through support vector machine-based algorithms and mass spectrometry-based feature selection, the study identified nine lipids (lysophosphatidylcholine 16:0, 18:0, and 20:4; phosphatidylcholine 16:0–18:1 , 16:0–18:2 , 18:0–18:1, 18:0–18:2 and 16:0–22:6; and triglycerides 16:0–18:1–18:1) as The most important feature detection in early stage cancer
.
Using these nine features, the study developed a liquid chromatography-mass spectrometry (MS)-based targeted assay using multiple reaction monitoring
.
This target assay achieved 100.
00% specificity in an independent validation cohort
.
The assay achieved over 90.
00% sensitivity and 92.
00% specificity in a hospital-based lung cancer screening cohort of 1036 participants examined by low-dose computed tomography and a prospective clinical cohort of 109 participants
.
Thus, matrix-assisted laser desorption/ionization MS imaging confirmed that selected lipids are differentially expressed in situ in early-stage lung cancer tissues
.
The method, named Lung Cancer Artificial Intelligence Detector, can be used for early detection of lung cancer or mass screening of high-risk groups for cancer prevention (click to read)
.
Phosphatase and tensin homolog (PTEN) is located on chromosome 10q23, encodes a 403 amino acid protein with phosphatase-dependent and phosphatase-independent functions, and is one of the most frequently mutated tumor suppressor genes in human cancers one
.
PTEN acts as a haploinsufficient tumor suppressor gene, and knockout of PTEN accelerates the progression of multiple human cancers
.
In addition to tumor suppression, PTEN plays critical roles in a variety of biological processes, including cell metabolism, cell motility, genome maintenance, and cellular senescence
.
The best-characterized function of canonical PTEN proteins is the ability to dephosphorylate PtdIns (3, 4, 5) P3 and convert it back to PIP2 in the cytoplasm, thus antagonizing the PI3K/AKT pathway that is primarily involved in cell regulation of growth, differentiation, proliferation, and Invasion
.
Recently, three conserved PTEN isoforms, PTENα (also known as PTEN-Long), PTENβ and PTENε, were sequentially identified
.
PTENα/β/ε have been shown to participate in different functional biological processes, such as mitophagy and neutrophil chemotaxis, through interactions with various proteins with N-terminal extended domains
.
Furthermore, results from different studies suggest that these PTEN isoforms display tumor suppressor or promotion effects by distinct mechanisms, further highlighting the complexity of the role of PTEN in tumor development
.
The study of PTENα/β/ε has improved the understanding of PTEN function
.
Nonetheless, the current exploration of canonical PTEN proteins and PTEN isoforms cannot fully account for the diversity of their involvement in biological processes and tumor development
.
Notably, the function of the noncoding RNAs produced by PTEN is unknown
.
Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules formed by back-splicing or skipping events from precursor mRNAs of thousands of genes in eukaryotes
.
Advances in RNA sequencing and bioinformatics tools have facilitated the discovery of various circRNAs and revealed their important functions
.
Functionally characterized circRNAs play key roles in gene regulation through various roles, including sponging microRNAs and proteins and regulating transcription and splicing
.
Compelling experimental evidence suggests that circRNAs are broadly involved in the initiation and progression of human cancers through their involvement in the regulation of one or more cancer hallmarks, including activation of invasion and metastasis, and that circRNAs are involved in the onset, spread, and progression of cancer.
Expression is often dysregulated
.
In addition, an increasing number of studies have shown that circRNA-based diagnostic and therapeutic strategies show great potential in cancer management
.
However, unlike miRNAs, the expression, roles, and molecular mechanisms of most circRNAs in regulating cancer progression remain largely unknown
.
Regarding the important role of circRNAs in tumorigenesis, the discovery and functional exploration of circRNAs is imminent
.
EIF4A3 inhibits circPTEN1 expression (figure from Molecular Cancer) Colorectal cancer (CRC) is one of the most common cancers in women and men worldwide
.
The development of CRC is a multi-step process involving multiple factors, such as genetic mutations
.
Despite advances in the diagnosis and treatment of the disease, the prognosis for patients with CRC remains poor
.
Clinically, metastasis is the leading cause of death in patients with CRC, and the liver is the most common site of distant metastases
.
The 5-year survival rate for patients with advanced CRC is only 12% due to distant tumor metastasis
.
This poor long-term survival outlook highlights that exploring the pathogenesis of CRC metastasis is urgent and essential for the treatment of CRC patients
.
Although previous studies have shown that circRNA abnormalities are closely related to the pathogenesis of CRC metastasis, the exact molecular mechanism remains unclear
.
In this study, a circRNA derived from the PTEN gene (circPTEN1) was identified as a suppressor of CRC progression
.
This study confirmed that circPTEN1 was significantly downregulated in CRC, and its expression was positively correlated with patient prognosis
.
This study further demonstrates that circPTEN1 inhibits CRC metastasis in vitro and in vivo
.
Mechanistically, circPTEN1 binds to the MH2 domain of Smad4 to disrupt the physical interaction between Smad4 and Smad2/3, thereby inhibiting Smad complex nuclear translocation and subsequent activation of downstream genes associated with EMT activation upon TGF-β stimulation.
Transcriptional activation
.
Therefore, circPTEN1 may be a potential therapeutic target for preventing CRC
.
The identification and functional exploration of circRNAs produced by PTEN has advanced the understanding of the diversity and complexity of PTEN function in physiological and pathological processes
.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-022-01495-y
.
Although the roles of canonical PTEN proteins and PTEN isoforms have been extensively explored, the current understanding of PTEN family members does not fully account for the diversity of their roles in biological processes and tumor development
.
Notably, the function of the noncoding RNAs produced by PTEN is unknown
.
On February 8, 2022, a research paper entitled "circPTEN1, a circular RNA generated from PTEN, suppresses cancer progression through inhibition of TGF-β/Smad signaling" was published online by Peking University Yin Yuxin's team in Molecular Cancer (IF=27).
The study identified a circular RNA produced by the PTEN gene, called circPTEN1, that is frequently downregulated in colorectal cancer, and that reduced expression of circPTEN1 predicts poorer survival
.
Low expression of circPTEN1 promoted metastasis in PDX models in vivo and accelerated cancer cell invasion in vitro, whereas overexpression of circPTEN1 exhibited the opposite effect
.
Mechanistically, this study found that circPTEN1 was able to bind the MH2 domain of Smad4 to disrupt its physical interaction with Smad2/3, thereby reducing Smad complex formation and subsequent nuclear translocation, and thus inhibited upon TGF-β stimulation Its expression of downstream genes associated with epithelial-mesenchymal transition
.
Furthermore, this study found that eIF4A3 inhibits the cyclization of circPTEN1 by directly binding to the flanking regions of circPTEN1
.
In conclusion, this study revealed a circRNA with tumor suppressor function produced by a novel PTEN gene, and further revealed the mechanism of circPTEN1 in TGF-β-mediated CRC metastasis
.
The identification of circPTEN1 provides a new direction for PTEN research, and elucidation of circPTEN1/TGF-β/Smad signaling may pave the way for the development of potential therapeutic strategies to inhibit cancer progression
.
In addition, on February 2, 2022, Yuxin Yin and Jun Wang of Peking University jointly published a study titled "Lung cancer scRNA-seq and lipidomics reveal aberrant lipid metabolism for early-stage diagnosis" in Science Translational Medicine (IF=17.
96).
In the paper, the study performed single-cell RNA sequencing of different early-stage lung cancers and found that lipid metabolism was widely dysregulated in different cell types, with glycerophospholipid metabolism being the most altered lipid metabolism-related pathway
.
Untargeted lipidomics was performed in an exploratory cohort of 311 participants
.
Through support vector machine-based algorithms and mass spectrometry-based feature selection, the study identified nine lipids (lysophosphatidylcholine 16:0, 18:0, and 20:4; phosphatidylcholine 16:0–18:1 , 16:0–18:2 , 18:0–18:1, 18:0–18:2 and 16:0–22:6; and triglycerides 16:0–18:1–18:1) as The most important feature detection in early stage cancer
.
Using these nine features, the study developed a liquid chromatography-mass spectrometry (MS)-based targeted assay using multiple reaction monitoring
.
This target assay achieved 100.
00% specificity in an independent validation cohort
.
The assay achieved over 90.
00% sensitivity and 92.
00% specificity in a hospital-based lung cancer screening cohort of 1036 participants examined by low-dose computed tomography and a prospective clinical cohort of 109 participants
.
Thus, matrix-assisted laser desorption/ionization MS imaging confirmed that selected lipids are differentially expressed in situ in early-stage lung cancer tissues
.
The method, named Lung Cancer Artificial Intelligence Detector, can be used for early detection of lung cancer or mass screening of high-risk groups for cancer prevention (click to read)
.
Phosphatase and tensin homolog (PTEN) is located on chromosome 10q23, encodes a 403 amino acid protein with phosphatase-dependent and phosphatase-independent functions, and is one of the most frequently mutated tumor suppressor genes in human cancers one
.
PTEN acts as a haploinsufficient tumor suppressor gene, and knockout of PTEN accelerates the progression of multiple human cancers
.
In addition to tumor suppression, PTEN plays critical roles in a variety of biological processes, including cell metabolism, cell motility, genome maintenance, and cellular senescence
.
The best-characterized function of canonical PTEN proteins is the ability to dephosphorylate PtdIns (3, 4, 5) P3 and convert it back to PIP2 in the cytoplasm, thus antagonizing the PI3K/AKT pathway that is primarily involved in cell regulation of growth, differentiation, proliferation, and Invasion
.
Recently, three conserved PTEN isoforms, PTENα (also known as PTEN-Long), PTENβ and PTENε, were sequentially identified
.
PTENα/β/ε have been shown to participate in different functional biological processes, such as mitophagy and neutrophil chemotaxis, through interactions with various proteins with N-terminal extended domains
.
Furthermore, results from different studies suggest that these PTEN isoforms display tumor suppressor or promotion effects by distinct mechanisms, further highlighting the complexity of the role of PTEN in tumor development
.
The study of PTENα/β/ε has improved the understanding of PTEN function
.
Nonetheless, the current exploration of canonical PTEN proteins and PTEN isoforms cannot fully account for the diversity of their involvement in biological processes and tumor development
.
Notably, the function of the noncoding RNAs produced by PTEN is unknown
.
Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules formed by back-splicing or skipping events from precursor mRNAs of thousands of genes in eukaryotes
.
Advances in RNA sequencing and bioinformatics tools have facilitated the discovery of various circRNAs and revealed their important functions
.
Functionally characterized circRNAs play key roles in gene regulation through various roles, including sponging microRNAs and proteins and regulating transcription and splicing
.
Compelling experimental evidence suggests that circRNAs are broadly involved in the initiation and progression of human cancers through their involvement in the regulation of one or more cancer hallmarks, including activation of invasion and metastasis, and that circRNAs are involved in the onset, spread, and progression of cancer.
Expression is often dysregulated
.
In addition, an increasing number of studies have shown that circRNA-based diagnostic and therapeutic strategies show great potential in cancer management
.
However, unlike miRNAs, the expression, roles, and molecular mechanisms of most circRNAs in regulating cancer progression remain largely unknown
.
Regarding the important role of circRNAs in tumorigenesis, the discovery and functional exploration of circRNAs is imminent
.
EIF4A3 inhibits circPTEN1 expression (figure from Molecular Cancer) Colorectal cancer (CRC) is one of the most common cancers in women and men worldwide
.
The development of CRC is a multi-step process involving multiple factors, such as genetic mutations
.
Despite advances in the diagnosis and treatment of the disease, the prognosis for patients with CRC remains poor
.
Clinically, metastasis is the leading cause of death in patients with CRC, and the liver is the most common site of distant metastases
.
The 5-year survival rate for patients with advanced CRC is only 12% due to distant tumor metastasis
.
This poor long-term survival outlook highlights that exploring the pathogenesis of CRC metastasis is urgent and essential for the treatment of CRC patients
.
Although previous studies have shown that circRNA abnormalities are closely related to the pathogenesis of CRC metastasis, the exact molecular mechanism remains unclear
.
In this study, a circRNA derived from the PTEN gene (circPTEN1) was identified as a suppressor of CRC progression
.
This study confirmed that circPTEN1 was significantly downregulated in CRC, and its expression was positively correlated with patient prognosis
.
This study further demonstrates that circPTEN1 inhibits CRC metastasis in vitro and in vivo
.
Mechanistically, circPTEN1 binds to the MH2 domain of Smad4 to disrupt the physical interaction between Smad4 and Smad2/3, thereby inhibiting Smad complex nuclear translocation and subsequent activation of downstream genes associated with EMT activation upon TGF-β stimulation.
Transcriptional activation
.
Therefore, circPTEN1 may be a potential therapeutic target for preventing CRC
.
The identification and functional exploration of circRNAs produced by PTEN has advanced the understanding of the diversity and complexity of PTEN function in physiological and pathological processes
.
Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-022-01495-y
