IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

Yang, Like; Yan, Bingrui; Qu, Lingmei; Ren, Jin; Li, Qiuying; Wang, Jingting; Kan, Xuan; Liu, Ming; Wang, Yakun; Sun, Yanan; Wang, Chao; Wang, Peng

doi:10.7150/ijbs.80921

Cited by 12 publications

(9 citation statements)

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“…Interestingly, after searching for any deregulated ribosome-related proteins besides Pelo, we found decreased levels of translation machinery associated 7 homolog (Tma7) and Endothelial differentiation-related factor 1(Edf1) in Hbs1l-deficient retina. Tma7 is a ubiquitously expressed protein that may inhibit autophagy by activating the PI3K/mTOR pathway (22), and Edf1 is reported to coordinate cellular responses to ribosome collisions (23, 24). In addition to rescuing the ribosomes stalled at the mRNA 3’ end (29), it remains to be elucidated if HBS1L/PELO may play a role in resolving collided ribosomes.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, apart from impacting its partner protein Pelo, Hbs1l depletion is accompanied with reduced levels of translation machinery associated 7 homolog (TMA7), and Endothelial differentiation-related factor 1(EDF1) proteins. While TMA7 is closely related to cell proliferation and autophagy (22), EDF1 is known to coordinate cellular responses to ribosome collisions (23, 24), when ribosomes slow down or completely stall when they encounter obstacles on mRNAs. Together these findings suggest a broad impact by the loss of Hbsl1 and its associated transcriptional regulators on key proteins for photoreceptor health and visual function.…”

Section: Introductionmentioning

confidence: 99%

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Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion

Luo,

Alwattar,

et al. 2023

Preprint

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Inherited retinal diseases (IRDs) encompass a genetically diverse group of conditions in which mutations in genes critical to retinal function lead to progressive loss of photoreceptor cells and subsequent visual impairment. A handful of ribosome-associated genes have been implicated in retinal disorders alongside neurological phenotypes. This study focuses on the HBS1L gene, encoding HBS1 Like Translational GTPase which has been recognized as a critical ribosomal rescue factor. Previously, we have reported a female child carrying biallelic HBS1L mutations, manifesting growth restriction, developmental delay, and hypotonia. In this study, we describe her ophthalmologic findings, compare them with the Hbs1ltm1a/tm1a hypomorph mouse model, and evaluate the underlying microscopic and molecular perturbations. The patient was noted to have impaired visual function observed by electroretinogram (ERG), with dampened amplitudes of a- and b-waves in both rod- and cone-mediated responses. Hbs1ltm1a/tm1a mice exhibited profound retinal thinning of the entire retina, specifically of the outer retinal photoreceptor layer, detected using in vivo imaging of optical coherence tomography (OCT) and retinal cross sections. TUNEL assay revealed retinal degeneration due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations in mass spectrometry analysis, with169 proteins increased and 480 proteins decreased including many critical IRD-related proteins. GO biological process and GSEA analyses reveal that these downregulated proteins are primarily involved in photoreceptor cell development, cilium assembly, phototransduction, and aerobic respiration. Furthermore, apart from the diminished level of PELO, a known partner protein, HBS1L depletion was accompanied by reduction in translation machinery associated 7 homolog (Tma7), and Endothelial differentiation-related factor 1(Edf1) proteins, the latter of which coordinates cellular responses to ribosome collisions. This novel connection between HBS1L and ribosome collision sensor (EDF1) further highlights the intricate mechanisms underpinning ribosomal rescue and quality control that are essential to maintain homeostasis of key proteins of retinal health, such as rhodopsin.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion

Luo,

Alwattar,

et al. 2023

Preprint

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“…IGF2BP3 has been associated with gastric cancer progression, with high expression in four gastric cancer subtypes indicating its potential role in promoting cell growth and invasion ( Zhou et al, 2017 ). Yang et al (2023) reported the oncogenic and poor prognostic properties of IGF2BP3 and provided evidence that downregulation of IGF2BP3 leads to enhanced apoptosis. Moreover, IGF2BP3 has been linked to cisplatin resistance in laryngeal cancer ( Yang et al, 2023 ), providing further evidence for the potential role of IGF2BP3 in cisplatin-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“… Yang et al (2023) reported the oncogenic and poor prognostic properties of IGF2BP3 and provided evidence that downregulation of IGF2BP3 leads to enhanced apoptosis. Moreover, IGF2BP3 has been linked to cisplatin resistance in laryngeal cancer ( Yang et al, 2023 ), providing further evidence for the potential role of IGF2BP3 in cisplatin-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Expression patterns of m6A RNA methylation regulators under apoptotic conditions in various human cancer cell lines

ALASAR,

SAĞLAM,

VATANSEVER

et al. 2024

Turkish Journal of Biology

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Background/aim Cancer is a complex disease that involves both genetic and epigenetic factors. While emerging evidence clearly suggests that changes in epitranscriptomics play a crucial role in cancer pathogenesis, a comprehensive understanding of the writers, erasers, and readers of epitranscriptomic processes, particularly under apoptotic conditions remains lacking. The aim of this study was to uncover the changes in the expression of m 6 A RNA modifiers under apoptotic conditions across various cancer cell lines. Materials and methods Initially, we quantified the abundance of m 6 A RNA modifiers in cervical (HeLa and ME180), breast (MCF7 and MDA-MB-231), lung (A549 and H1299), and colon (Caco-2 and HCT116) cancer cell lines using qPCR. Subsequently, we induced apoptosis using cisplatin and tumor necrosis factor-alpha (TNF-α) to activate intrinsic and extrinsic pathways, respectively, and assessed apoptosis rates via flow cytometry. Further, we examined the transcript abundance of m 6 A RNA modifiers under apoptotic conditions in cervical, breast, and lung cancer cell lines using qPCR. Results Overall, treatment with cisplatin increased the abundance of m 6 A modifiers, whereas TNF-α treatment decreased their expression in cervical, breast, and lung cancer cell lines. Specifically, cisplatin-induced apoptosis, but not TNF-α-mediated apoptosis, resulted in decreased abundance of METTL14 and FTO transcripts. Additionally, cisplatin treatment drastically reduced the abundance of IGF2BP2 and IGF2BP3 readers. Conclusion These results suggest that the differential response of cancer cells to apoptotic inducers may be partially attributed to the expression of m 6 A RNA modifiers.

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“…Initial observations suggest that PI3K/AKT/mTOR signaling pathway plays an important role in the anti-autophagy effect [ 163 ]. IGF2BP3 promotes translation machinery associated 7 homolog (TMA7) mRNA stability and translation through recognition of the m 6 A site on the TMA7 3’-UTR, which in turn activates the PI3K/AKT/mTOR pathway and ultimately inhibits autophagy [ 164 ]. Conversely, activating transcription factor 4 (ATF4) negatively regulates the mTOR signaling pathway.…”

Section: The Indirect Regulatory Role Of M 6 a Met...mentioning

confidence: 99%

Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis

Bi,

Liu,

et al. 2023

Aging

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Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is characterized by high morbidity and mortality and one of the major diseases that seriously hang over global human health. Autophagy is a crucial regulator in the complicated pathophysiological processes of sepsis. The activation of autophagy is known to be of great significance for protecting sepsis induced organ dysfunction. Recent research has demonstrated that N6-methyladenosine (m 6 A) methylation is a well-known post-transcriptional RNA modification that controls epigenetic and gene expression as well as a number of biological processes in sepsis. In addition, m 6 A affects the stability, export, splicing and translation of transcripts involved in the autophagic process. Although it has been suggested that m 6 A methylation regulates the biological metabolic processes of autophagy and is more frequently seen in the progression of sepsis pathogenesis, the underlying molecular mechanisms of m 6 A-modified autophagy in sepsis have not been thoroughly elucidated. The present article fills this gap by providing an epigenetic review of the processes of m 6 A-modified autophagy in sepsis and its potential role in the development of novel therapeutics.

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IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation

Cited by 12 publications

References 50 publications

Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion

Genetic deficiency of ribosomal rescue factor HBS1L causes retinal dystrophy associated with Pelota and EDF1 depletion

Expression patterns of m6A RNA methylation regulators under apoptotic conditions in various human cancer cell lines

Novel insights into the regulatory role of N6-methyladenosine methylation modified autophagy in sepsis

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