MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells

Yeh, Da‐Wei; Zhao, Xuyao; Siddique, Hifzur R.; Zheng, Mengmei; Choi, Hye Yeon; Machida, Tatsuya; Narayanan, Priya; Kou, Yi; Punj, Vasu; Tahara, Stanley M.; Feldman, Douglas E.; Chen, Lin; Machida, Keigo

doi:10.1038/s41420-023-01427-9

Cited by 9 publications

(3 citation statements)

References 28 publications

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“…Recent work has shown that MSI2 can bind to Internal Ribosome Entry Sites (IRES) located in the 5'UTRs of oncogenic mRNAs including MYC, JUN and VEGFA promoting protein expression by increasing translation. 14 Interestingly, LEF-1 also includes a potential IRES in its 5'UTR, 15 which coupled to our data suggest that MSI2 (together β-catenin) might bind the 5'UTR IRES of LEF1 to enhance its translation. This study further highlights novel roles for β-catenin in the RBP/RNA biology of haematopoietic cells which could be an important axis regulating human Toska, Lorraine Shah-Goodwin and Caroline Humphreys, for the collection of human umbilical cord blood.…”

supporting

confidence: 64%

β-Catenin associates with a Wnt signaling mRNA network in myeloid cells through canonical RBP binding

Wagstaff,

Sevim,

Goff

et al. 2024

Preprint

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Wnt/β-catenin signaling is important for normal hematopoietic stem/progenitor cell (HSPC) biology and heavily implicated in many hematological malignancies. The central mediator, β-catenin, is an attractive therapeutic target in myeloid neoplasms however, the design of targeted agents has been hampered by a limited understanding of its molecular interactions in hematopoietic cells. To address this shortfall, we recently published the first β-catenin interactome (Morgan et al, 2019) in haematological cells and identified a plethora of novel partners which included the significant enrichment of RNA binding proteins (Wagstaff et al, 2022), including Musashi-2 (MSI2). MSI2 has been extensively implicated in normal HSC activity and also promotes aggressive myeloid leukemias where its expression confers inferior survival. Interaction between MSI2 and Wnt signalling has not previously been reported in a hematopoietic context. In this study we identify an interaction between MSI2 and β-catenin in both myeloid cell lines and primary AML patient samples where there is a significant degree of correlation between the proteins. We demonstrate that MSI2 can impact Wnt signalling output (TCF/LEF activity) through modulating LEF-1 expression and localization, and that MSI2 can further bind LEF1 transcript, an interaction augmented by β-catenin. Finally, we show that MSI2 mediated expansion of HSPCs could be partly driven through LEF1 regulation. To our knowledge this is the first study to demonstrate an interaction between MSI2 and β-catenin in haematopoietic cells, and shows the potential for β-catenin to cooperate with RBPs to govern HSPC proliferation. Finally, these data indicate β-catenin may also serve critical post-transcriptional functions (in addition to transcriptional roles) in haematopoietic cells, which could extend to regulating expression of Wnt signalling components.

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supporting

confidence: 64%

β-Catenin associates with a Wnt signaling mRNA network in myeloid cells through canonical RBP binding

Wagstaff,

Sevim,

Goff

et al. 2024

Preprint

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“…RNA binding proteins (RBPs) can bind with transcript or non-transcript RNAs (11,12). In addition, eukaryotic translation initiation factor 4A3 (EIF4A3) is a member of RBPs, which is able to act as an oncogene in ESCA (13).…”

Section: Introductionmentioning

confidence: 99%

LncRNA SSTR5-AS1 promotes esophageal carcinoma through regulating ITGB6/JAK1/STAT3 signaling

Tang,

Jiang,

Zong

et al. 2023

Preprint

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Background Esophageal carcinoma (ESCA) is the aggressive cancer which threatens people’s health. LncRNA SSTR5-AS1 is upregulated in ESCA. However, the potential regulatory mechanism of SSTR5-AS1 in ESCA is unknown. Methods GEPIA was used to explore the prognosis of SSTR5-AS1 in ESCA patients. EdU staining was used to detect cell proliferation. Transwell assay was applied for assessing cell invasion and migration. Meanwhile, RNA pull-down and RIP were applied to assess the relationship among SSTR5-AS1, EIF4A3 and ITGB6, and FISH was applied for exploring the localization of SSTR5-AS1 in ESCA cells. Results SSTR5-AS1 was upregulated in ESCA. SSTR5-AS1 downregulation repressed the invasion and migration of ESCA cells, and promoted cells apoptosis. Furthermore, SSTR5-AS1 shRNA upregulated the levels of Bax, cleaved caspase 3 and inhibited p-STAT3, p-JAK1 and Bcl-2 levels. SSTR5-AS1 was distributed in cytoplasm, and it could regulate ITGB6 by interacting with EIF4A3. SSTR5-AS1 silencing inhibited ITGB6 expression and inactivated JAK1/STAT3 signaling, while EIF4A3 upregulation reversed this phenomenon. In addition, SSTR5-AS1 silencing attenuated the malignant behavior of ESCA cells through ITGB6-mediated JAK1/STAT3 signaling. Conclusion SSTR5-AS1 promotes ESCA development through interacting with EIF4A3 to regulate ITGB6/JAK1/STAT3 signaling. Hence, this research supplied a basis for discovering strategies against ESCA.

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“…Non-coding RNAs (ncRNAs) modulate expression patterns of various genes, which play important roles in different diseases. Several studies have unraveled associations between aberrant ncRNA expressions and pathologies of human diseases ( Singh et al, 2020 ; Yeh et al, 2023 ). Like other ncRNAs, recently discovered ncRNAs, circular RNAs (circRNAs) have also been found to play an important role in gene regulation via interaction with other biomolecules like nucleic acids, proteins, and microRNAs (miRNAs).…”

mentioning

confidence: 99%

Editorial: Genes, diseases, immunity and immunogenomics

Siddique

2023

Front. Genet.

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MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells

Cited by 9 publications

References 28 publications

β-Catenin associates with a Wnt signaling mRNA network in myeloid cells through canonical RBP binding

β-Catenin associates with a Wnt signaling mRNA network in myeloid cells through canonical RBP binding

LncRNA SSTR5-AS1 promotes esophageal carcinoma through regulating ITGB6/JAK1/STAT3 signaling

Editorial: Genes, diseases, immunity and immunogenomics

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