ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

Wang, Lihong; Yuan, Ye; Wang, Jiao; Luo, Ying; Yang, Lan; Ge, Jia; Li, Lei; Liu, Feng; Deng, Qi; Yan, Zexuan; Liang, Mei; Wei, Sen; Liu, Xindong; Wang, Yan; Ping, Yi‐Fang; Shi, Yu; Yu, Shanshan; Zhang, Xia; Cui, You‐Hong; Yao, Xiaohong; Huang, Feng; Luo, Tao; Bian, Xiu‐Wu

doi:10.1002/advs.202105938

Cited by 11 publications

(3 citation statements)

References 42 publications

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“…Most reports on its regulation of tumour stemness have appeared in colon cancer and in gliomas. For example, Wang, Li-Hong et al reported that ASCL2 can control the tumour stemness phenotype of glioma cells by regulating the expression of ATG9 protein in glioma cells [ 19 ]. It has also been reported that ASCL2 is highly expressed in mismatch repair-sufficient or microsatellite-stabilised colon cancers and can maintain the stemness of colon cancer tumour cells and activate cancer-associated fibroblasts through the activity of transcription factors, thereby inducing an immune-rejecting microenvironment to inhibit the infiltration of immune cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer

Li,

Chen,

et al. 2024

Aging

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Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A’s implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.

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Section: Discussionmentioning

confidence: 99%

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer

Li,

Chen,

et al. 2024

Aging

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“…The evidence suggests that the capacity for self-renewal and proliferation of CSC can cause metastasis and therapeutic resistance of cancer, leading to recurrence and death in patients [23,24]. More importantly, autophagy is proposed to maintain stemness phenotype in cancer [25]. Notably the therapeutic mechanisms of miR-145-5p were systematically studied, regarding the signaling pathway, effect on LCSC self-renewal activity, and the speci c role in autophagy, for which a variety of techniques including reverse transcription PCR (RT-PCR), western blot, transwell and cell sphere experiments.…”

Section: Introductionmentioning

confidence: 99%

Liposome-lentivirus hybrid carriers for miRNA therapy of liver cancer stem cells with molecular mechanism study on tumor progression hamper effects

Sun,

Chen,

Dai

et al. 2024

Preprint

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Background: Cancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability. Methods: We have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs). Results: MRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3β at ser 9 (p-GSK-3β S9) to inactivate GSK3β, and facilitate translocation of β-catenin into the nucleus to activate the Wnt/β-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3β/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs. Conclusions: These findings provide novel insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery.

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“…Furthermore, the therapeutic efficacy of MRL145 in eradicating LCSCs was also evaluated. The evidence suggests that autophagy is proposed to maintain stemness phenotype in cancer [ 35 ]. Notably the therapeutic mechanisms of miR-145-5p were systematically studied, regarding the signaling pathway, effect on LCSC self-renewal activity, and the specific role in autophagy.…”

Section: Introductionmentioning

confidence: 99%

Liposome-lentivirus for miRNA therapy with molecular mechanism study

Sun,

Chen,

Dai

et al. 2024

J Nanobiotechnol

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Background Cancer stem cells (CSCs) play a vital role in the occurrence, maintenance, and recurrence of solid tumors. Although, miR-145-5p can inhibit CSCs survival, poor understanding of the underlying mechanisms hamperes further therapeutic optimization for patients. Lentivirus with remarkable transduction efficiency is the most commonly used RNA carrier in research, but has shown limited tumor-targeting capability. Methods We have applied liposome to decorate lentivirus surface thereby yielding liposome-lentivirus hybrid-based carriers, termed miR-145-5p-lentivirus nanoliposome (MRL145), and systematically analyzed their potential therapeutic effects on liver CSCs (LCSCs). Results MRL145 exhibited high delivery efficiency and potent anti-tumor efficacy under in vitro and in vivo. Mechanistically, the overexpressed miR-145-5p can significantly suppress the self-renewal, migration, and invasion abilities of LCSCs by targeting Collagen Type IV Alpha 3 Chain (COL4A3). Importantly, COL4A3 can promote phosphorylating GSK-3β at ser 9 (p-GSK-3β S9) to inactivate GSK3β, and facilitate translocation of β-catenin into the nucleus to activate the Wnt/β-catenin pathway, thereby promoting self-renewal, migration, and invasion of LCSCs. Interestingly, COL4A3 could attenuate the cellular autophagy through modulating GSK3β/Gli3/VMP1 axis to promote self-renewal, migration, and invasion of LCSCs. Conclusions These findings provide new insights in mode of action of miR-145-5p in LCSCs therapy and indicates that liposome-virus hybrid carriers hold great promise in miRNA delivery. Graphical abstract

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ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor

Cited by 11 publications

References 42 publications

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer

Liposome-lentivirus hybrid carriers for miRNA therapy of liver cancer stem cells with molecular mechanism study on tumor progression hamper effects

Liposome-lentivirus for miRNA therapy with molecular mechanism study

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