Oncogenic Ras suppresses ING4-TDG-Fas axis to promote apoptosis resistance

Sun, Jie; Shen, Qi; Lu, Haiqi; Jiang, Zhinong; Xu, Wenxia; Feng, Lifeng; Li, Ling; Wang, Xian; Cai, Xiujun; Jin, Hongchuan

doi:10.18632/oncotarget.6015

Cited by 6 publications

(4 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Downregulation of TDG is verified in pancreatic cancer cells with KRAS mutations, in contrast to those expressing the wild-type isoform of KRAS . Furthermore, TDG expression levels are restored after KRAS knockdown [ 80 , 81 ].…”

Section: Kras Role On Apoptotic Cell Deathmentioning

confidence: 99%

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Ferreira

Pereira

Reis

et al. 2022

Cells

View full text Add to dashboard Cite

KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment. In order to inhibit apoptosis, these oncogenic mutations were reported to upregulate anti-apoptotic proteins, including Bcl-xL and survivin, and to downregulate proteins related to apoptosis induction, including thymine-DNA glycosylase (TDG) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). In addition, KRAS mutations are known to induce autophagy in order to promote cell survival and tumor progression through MAPK and PI3K regulation. Thus, these mutations confer resistance to anti-cancer drug treatment and, consequently, result in poor prognosis. Several therapies have been developed in order to overcome KRAS-induced cell death resistance and the downstream signaling pathways blockade, especially by combining MAPK and PI3K inhibitors, which demonstrated promising results. Understanding the involvement of KRAS mutations in apoptosis and autophagy regulation, might bring new avenues to the discovery of therapeutic approaches for CRCs harboring KRAS mutations.

show abstract

Section: Kras Role On Apoptotic Cell Deathmentioning

confidence: 99%

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Ferreira

Pereira

Reis

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…3 (e)). With apoptotic behaviors of BCL2 and the Ras family [42] , [43] , we conjecture that the subpathway regulates both estrogen receptor activity and cell apoptosis in breast cancer cells.…”

Section: Resultsmentioning

confidence: 96%

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

Lee,

Park,

Piao

et al. 2024

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

“…These results suggest that miR-181c is a regulator of FAS mediated apoptosis in Ewing’s sarcoma. FAS plays a central role in the physiological regulation of apoptosis, and has been implicated in the pathogenesis of various malignancies [ 21 – 23 ]. Our data suggests that FAS is one of the crucial factors that enhance tumor proliferation in ES, as well as other malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing’s sarcoma cells

et al. 2018

View full text Add to dashboard Cite

BackgroundMicroRNAs (miRNAs) are endogenous, small non-coding RNAs that play important roles in multiple biological processes. Here, we show that miRNAs play an important function in the down-regulation of FAS expression in Ewing’s sarcoma (ES) cells.MethodsTo identify and characterize possible oncogenic factors in ES, we employed a microarray-based approach to profile the changes in the expression of miRNAs and their target mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs).ResultsMiRNA, miR-181c, was significantly up-regulated, whereas FAS receptor expression was significantly down-regulated in all tested ES cells compared with hMSCs. Introducing anti-miR-181c into ES cell lines resulted in an increased expression of FAS2. Additionally, anti-miR-181c prohibited cell growth and cell cycle progression in ES cells. Anti-miR-181c also promoted apoptosis in ES cells. Furthermore, the down-regulation of miR-181c in ES cells significantly suppressed tumor growth in vivo.ConclusionsThese results suggest that unregulated expression of miR-181c could contribute to ES by targeting FAS. Reduction of miR181c increased expression of FAS. This proves that retardation of cell cycle progression removes apoptosis resistance, thereby repressing the growth of Ewing sarcoma. Since FAS signaling is involved in regulation of apoptosis and tumor proliferation, our findings might contribute to new therapeutic targets for ES.

show abstract

Oncogenic Ras suppresses ING4-TDG-Fas axis to promote apoptosis resistance

Cited by 6 publications

References 35 publications

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Multi-layered knowledge graph neural network reveals pathway-level agreement of three breast cancer multi-gene assays

MicroRNA-181c prevents apoptosis by targeting of FAS receptor in Ewing’s sarcoma cells

Contact Info

Product

Resources

About