High-grade gliomas such as glioblastoma (GBM) are common intracranial tumors, with high mortality and extremely poor prognosis. There have been breakthroughs in the treatment of gliomas in recent years, but the overall survival can only be extended for several months. A series of

glioblastoma (GBM) are common intracranial tumors, with high mortality and extremely poor prognosis. There have been breakthroughs in the treatment of gliomas in recent years, but the overall survival can only be extended for several months. A series of oncogene expression and dysfunction are closely related to the occurrence and development of gliomas. The current research focuses on exploring new key signaling pathways and molecular targets.

Cao Cong's research has confirmed over the years that G protein inhibitory α subunits 1 and 3 (Gαi1/3 protein) are key molecules in multiple signaling pathways. Under the stimulation of multiple cells and growth factor , Gαi1/3 protein binds receptors such as receptor tyrosine kinases (RTKs), and mediates the downstream signals (PI3K-Akt-mTOR and Erk-MAPK, etc.) to transduce ( Science Advances 2022 [1], PNAS 2018 [2], Protein Cell 2022a/b [3, 4], Science Signaling, 2009 [5], Oncogene2018, 2021 [6, 7], IJBS 2022 [8], Theranostics 2018, 2021a/b [9-11] and other papers) . Previous studies of the research team found that the expression of Gαi1/3 in tumor tissue specimens of glioma patients was significantly upregulated; knockdown and knockout of Gαi1/3 can significantly inhibit the growth of glioma cells in vitro and intracranially in mice ( Oncogene2018 [6], Theranostics 2021a [9]) . However, the molecular mechanism of Gαi1/3 protein expression regulation is not clear. YME1L (YME1 Like 1 ATPase) is a major member of the AAA family ATPase and is located in the inner mitochondrial membrane [12]. YME1L is crucial for maintaining the morphology, function and plasticity of mitochondrial [13]. YME1L is assembled into homologous oligomers in the inner membrane of the mitochondria and is involved in the degradation of mitochondrial proteins: including lipid transporters, mitochondrial translocation proteins and OPA1; the loss of YME1L leads to increased mitochondrial division and mitochondrial fragmentation; YME1L also participates in the proliferation of cells in and inhibits apoptosis [13]. However, the expression and potential function of YME1L in human gliomas remains unclear.

On October 19, 2022, Sozhou University Cao Cong ProteinCellProteinCellYME1L overexpression exerts pro-tumorigenic activity in glioma by promoting Gαi1 expression and Akt activation research paper, This study reveals that YME1L promotes glioma cell growth by promoting Gαi1 protein expression and downstream Akt activation.

1 combined with TCGA database and patient tissue specimens found that YME1L expression was significantly upregulated in glioma tissue and was enriched only in mitochondria. In human glioma cells cultured in vitro, knockdown of YME1L by viral shRNA knockdown or CRISPR/Cas9 method significantly inhibits cell growth, proliferation and migration, and induces cell mitochondrial damage and cell apoptosis; while overexpressing YME1L by viral vector promotes glioma cell growth. Mechanism study found that after knockdown and knockdown of YME1L in glioma cells, Gαi1 expression is downregulated and downstream Akt is inhibited; and after overexpressing YME1L, Gαi1 expression level increases and Akt is activated.

Gαi1 overexpression or introduction of continuously activated Akt (caAkt1) reduces the anti-glioma cell effect after YME1L knockdown. In vivo studies found that human glioma cells after YME1L knockdown significantly inhibited intracranial growth of mice; Gαi1 expression in tumor tissues was downregulated and Akt activation was inhibited. In summary, YME1L activates glioma cell growth by mediating Gαi1-Akt signal, and this pathway may be an important new therapeutic target for gliomas.High-grade gliomas such as

glioblastoma (GBM) are common intracranial tumors, with high mortality and extremely poor prognosis. There have been breakthroughs in the treatment of gliomas in recent years, but the overall survival can only be extended for several months. A series of oncogene expression and dysfunction are closely related to the occurrence and development of gliomas. The current research focuses on exploring new key signaling pathways and molecular targets.

Cao Cong's research has confirmed over the years that G protein inhibitory α subunits 1 and 3 (Gαi1/3 protein) are key molecules in multiple signaling pathways. Under the stimulation of multiple cells and growth factor , Gαi1/3 protein binds receptors such as receptor tyrosine kinases (RTKs), and mediates the downstream signals (PI3K-Akt-mTOR and Erk-MAPK, etc.) to transduce ( Science Advances 2022 [1], PNAS 2018 [2], Protein Cell 2022a/b [3, 4], Science Signaling, 2009 [5], Oncogene2018, 2021 [6, 7], IJBS 2022 [8], Theranostics 2018, 2021a/b [9-11] and other papers) . Previous studies of the research team found that the expression of Gαi1/3 in tumor tissue specimens of glioma patients was significantly upregulated; knockdown and knockout of Gαi1/3 can significantly inhibit the growth of glioma cells in vitro and intracranially in mice ( Oncogene2018 [6], Theranostics 2021a [9]) . However, the molecular mechanism of Gαi1/3 protein expression regulation is not clear. YME1L (YME1 Like 1 ATPase) is a major member of the AAA family ATPase and is located in the inner mitochondrial membrane [12]. YME1L is crucial for maintaining the morphology, function and plasticity of mitochondrial [13]. YME1L is assembled into homologous oligomers in the inner membrane of the mitochondria and is involved in the degradation of mitochondrial proteins: including lipid transporters, mitochondrial translocation proteins and OPA1; the loss of YME1L leads to increased mitochondrial division and mitochondrial fragmentation; YME1L also participates in the proliferation of cells in and inhibits apoptosis [13]. However, the expression and potential function of YME1L in human gliomas remains unclear.

On October 19, 2022, Sozhou University Cao Cong ProteinCellProteinCellYME1L overexpression exerts pro-tumorigenic activity in glioma by promoting Gαi1 expression and Akt activation research paper, This study reveals that YME1L promotes glioma cell growth by promoting Gαi1 protein expression and downstream Akt activation.

1 combined with TCGA database and patient tissue specimens found that YME1L expression was significantly upregulated in glioma tissue and was enriched only in mitochondria. In human glioma cells cultured in vitro, knockdown of YME1L by viral shRNA knockdown or CRISPR/Cas9 method significantly inhibits cell growth, proliferation and migration, and induces cell mitochondrial damage and cell apoptosis; while overexpressing YME1L by viral vector promotes glioma cell growth. Mechanism study found that after knockdown and knockdown of YME1L in glioma cells, Gαi1 expression is downregulated and downstream Akt is inhibited; and after overexpressing YME1L, Gαi1 expression level increases and Akt is activated.

Gαi1 overexpression or introduction of continuously activated Akt (caAkt1) reduces the anti-glioma cell effect after YME1L knockdown. In vivo studies found that human glioma cells after YME1L knockdown significantly inhibited intracranial growth of mice; Gαi1 expression in tumor tissues was downregulated and Akt activation was inhibited. In summary, YME1L activates glioma cell growth by mediating Gαi1-Akt signal, and this pathway may be an important new therapeutic target for gliomas.

Original link: https://doi.org/10.1093/procel/pwac011

Reference

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