High expression of immunity-related GTPase family M protein in glioma promotes cell proliferation and autophagy protein expression

Xu, Yanwen; Liu, Renli; Liao, Chuanpeng; Liu, Jing; Zhao, Hua; Li, Zongyang; Liu, Wenlan; Chen, Lei; Wu, Changpeng; Tan, Hui; Chen, Zhongping; Xie, Ni; Li, Weiping

doi:10.1016/j.prp.2018.10.004

Cited by 6 publications

(6 citation statements)

References 20 publications

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“…Although the links between IRGM and autophagic machinery are well-established in inflammatory and infectious diseases, the contributions of IRGM to autophagy in tumor progression have remained unclear. To date, IRGM has only been observed to promote tumor development in hepatocellular carcinoma, gastric cancer (44), melanomas and gliomas (45). Knockdown of IRGM can suppress the expressions of LC3 II and p62 in gliomas (45) and melanomas (46), and it is also shown to inhibit the expression of LC3 II and ATGs , such as ATG5, ATG12 and ATG3 in hepatocellular carcinoma (47).…”

Section: Discussionmentioning

confidence: 99%

“…To date, IRGM has only been observed to promote tumor development in hepatocellular carcinoma, gastric cancer (44), melanomas and gliomas (45). Knockdown of IRGM can suppress the expressions of LC3 II and p62 in gliomas (45) and melanomas (46), and it is also shown to inhibit the expression of LC3 II and ATGs , such as ATG5, ATG12 and ATG3 in hepatocellular carcinoma (47). In our study, we observed that knockdown of Cav1 abrogated IRGM expression, while IRGM overexpression reversed the downregulation of LC3 II, Beclin-1 and p62 caused by the knockdown of Cav1 expression.…”

Section: Discussionmentioning

confidence: 99%

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Caveolin-1 promotes radioresistance via IRGM-regulated autophagy in lung cancer

et al. 2021

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Background: Radiotherapy is the standard therapeutic approach for non-small cell lung cancers (NSCLCs). However, radiotherapy resistance accounts for major treatment failures in NSCLC patients.Recently, targeting autophagy-related signaling has shown potential to improve radiotherapy. Furthermore, some studies have reported that caveolin-1 (Cav1), a primary scaffolding protein of caveolae, is positively associated with NSCLC progression and cell autophagy. However, the function of Cav1-mediated autophagy in NSCLC radioresistance remains largely unknown. Methods: The NSCLC irradiation (IR)-resistant cell lines H358-IRR and A549-IRR were used for in vitro analysis. Real-time quantitative PCR (qPCR), western blot, cell counting kit-8 (CCK-8), colony formation and transmission electron microscopy analyses were performed to explore the relationship between Cav1 and immunity-related GTPase family M protein (IRGM)-regulated autophagy in the radiation resistance of lung cancers. Results: Cav1 was significantly overexpressed in H358-IRR and A549-IRR cells compared to their parental counterparts. Knockdown of Cav1 significantly decreased the proliferation of IR-resistant NSCLC cells. Combinational treatment of IR and siRNA of Cav1 showed enhanced inhibition of the cell viability and colony formation of IR-resistant NSCLC cells. In addition, Cav1 overexpression could upregulate the autophagic proteins microtubule associated protein 1 light chain 3 II (LC3 II), Beclin-1 and Sequestosome 1 (SQSTM1/p62) in parental NSCLC cells, while Cav1 downregulation by siRNA inhibited the expression of LC3 II, Beclin-1 and p62 and the formation of autophagosomes in IR-resistant NSCLC cells. Furthermore, we observed that IRGM was downregulated after knockdown of Cav1 in IR-resistant NSCLC cells. Thus, Cav1 was observed to promote autophagy and increase IR-resistant cell survival by targeting IRGM. Conclusions:The results of our study showed that Cav1 is involved in the development of IR resistance in NSCLC through IRGM-regulated autophagy and can be considered as a potential therapeutic target for improving the radiosensitivity of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Caveolin-1 promotes radioresistance via IRGM-regulated autophagy in lung cancer

et al. 2021

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“…IRGM appears to be a fulcrum between immunity and tumorigenesis. Studies on melanoma [16,30], hepatocellular carcinoma [31], glioma [32], and gastric cancer [33] have shown that IRGM can promote carcinogenesis. In human glioma cell lines, overexpression of IRGM was linked to increased cell colony formation, cell proliferation, and Akt activation [32].…”

Section: Irgm In Cancermentioning

confidence: 99%

“…Studies on melanoma [16,30], hepatocellular carcinoma [31], glioma [32], and gastric cancer [33] have shown that IRGM can promote carcinogenesis. In human glioma cell lines, overexpression of IRGM was linked to increased cell colony formation, cell proliferation, and Akt activation [32]. Xu et al [34] also established that highly expressed IRGM in glioma cells promoted IL-8 production and M2 macrophage polarization via p62/TRAF6/NK-κB signalling.…”

Section: Irgm In Cancermentioning

confidence: 99%

Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis

2022

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The human immunity-related GTPase M (IRGM) is a GTP-binding protein that regulates selective autophagy including xenophagy and mitophagy. IRGM impacts autophagy by (1) affecting mitochondrial fusion and fission, (2) promoting the co-assembly of ULK1 and Beclin 1, (3) enhancing Beclin 1 interacting partners (AMBRA1, ATG14L1, and UVRAG), (4) interacting with other key proteins (ATG16L1, p62, NOD2, cGAS, TLR3, and RIG-I), and (5) regulating lysosomal biogenesis. IRGM also negatively regulates NLRP3 inflammasome formation and therefore, maturation of the important pro-inflammatory cytokine IL-1β, impacting inflammation and pyroptosis. Ultimately, this affords protection against chronic inflammatory diseases. Importantly, ten IRGM polymorphisms (rs4859843, rs4859846, rs4958842, rs4958847, rs1000113, rs10051924, rs10065172, rs11747270, rs13361189, and rs72553867) have been associated with human inflammatory disorders including cancer, which suggests that these genetic variants are functionally relevant to the autophagic and inflammatory responses. The current review contextualizes IRGM, its modulation of autophagy, and inflammation, and emphasizes the role of IRGM as a cross point of immunity and tumorigenesis.

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“…In AGBL2-overexpressing hepatocellular carcinoma cells, IRGM-mediated autophagy promoted cancer cell survival and proliferation [73]. Recent reports revealed that IRGM was upregulated in human glioma and functioned in glioma cell proliferation and autophagy [74]. Other studies showed the involvement of ATG7 and JNK2 in the connection with the autophagy-inflammasome pathway in the experimental model of cancers [75,76].…”

Section: Autophagy-related Moleculesmentioning

confidence: 99%

Crosstalks between inflammasome and autophagy in cancer

et al. 2020

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Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anticancer strategies, although it remains underexplored in terms of their crosstalks.

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High expression of immunity-related GTPase family M protein in glioma promotes cell proliferation and autophagy protein expression

Cited by 6 publications

References 20 publications

Caveolin-1 promotes radioresistance via IRGM-regulated autophagy in lung cancer

Caveolin-1 promotes radioresistance via IRGM-regulated autophagy in lung cancer

Immunity-related GTPase IRGM at the intersection of autophagy, inflammation, and tumorigenesis

Crosstalks between inflammasome and autophagy in cancer

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