Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer

Wang, Lu; Xiong, Xi; Yao, Ziting; Zhu, Jianlin; Lin, Yusheng; Lin, Wan-Wan; Li, Kai; Xu, Xiaozheng; Guo, Yi; Chen, Yuping; Pan, Yunlong; Zhou, Fuyou; Fan, Jun; Yan, Chen; Gao, Shegan; Yeung, Sai Ching Jim; Zhang, Hao

doi:10.1016/j.canlet.2020.10.052

Cited by 19 publications

(24 citation statements)

References 46 publications

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“…Discovery of chiRNAs has added a novel layer of complex RNA universe and provided insights into molecular mechanisms of human diseases. Results from numerous studies suggest that chiRNAs not only play important roles in cancer pathogenesis but also can serve as biomarkers and therapeutic targets [ 10 , 11 , 12 , 22 , 23 , 24 , 25 ]. Different tools tailored explicitly to chiRNA research have been developed [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Without the tamoxifen-inducible A-P as chiRNA KI mouse model, we were able to show that A-P as chiRNA is highly enriched in ESCC [ 11 ], while whether the enriched expression of A-P as chiRNA is the causation or resultant of ESCC pathogenesis is still unknown. The inducible model enabled us to show the role of A-P as chiRNA in 4NQO-induced ESCC initiation, evidenced by the increased number of the tumor compared with WT mice.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously investigated the potentials of chiRNAs as biomarkers and molecular targets in cancer [ 10 , 11 , 12 ]. We examined salivary exosomal GOLM1-NAA35 chiRNA (se G-N chiRNA) in patients with esophageal squamous cell carcinoma (ESCC) and found that se G-N chiRNA can serve as a convenient, reliable, and noninvasive biomarker for the assessment of therapeutic response and recurrence [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Results derived from xenograft models indicate that A-P as chiRNA can promote ESCC cell spread to lymph nodes and enhance stemness through modulating OCT4. Mechanistically, A-P as chiRNA induces cancer stemness by activating extracellular-signal-regulated kinase 5 (ERK5)-mediated non-canonical RNA Polymerase II-Associated Factor 1 Homolog (PAF1) [ 11 ]. These findings suggest that chiRNAs could play critical roles in cancer pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Luo

Yao

et al. 2022

Cells

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Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-PaschiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Luo

Yao

et al. 2022

Cells

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“…Immunoblotting was performed as described previously ( Gan et al, 2016 ; Du et al, 2019 ; Xiong et al, 2020 ; Wang et al, 2021b ). Briefly, total proteins were extracted from the breast cancer cells or exosomes on ice with radioimmunoprecipitation assay (RIPA) cell lysis buffer supplemented with protease inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

Dong

Xie

Jiang

et al. 2021

Front. Cell Dev. Biol.

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Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.

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Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles

Xiong

Wang

et al. 2022

J of Extracellular Vesicle

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Chimeric RNA ASTN2-PAPPAas aggravates tumor progression and metastasis in human esophageal cancer

Cited by 19 publications

References 46 publications

Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

Neoantigen‐based cancer vaccination using chimeric RNA‐loaded dendritic cell‐derived extracellular vesicles

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