Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

Li, Xiaoping; Xiao, Yunshuo; Wang, Xiaoqi; Huang, Ruihao; Wang, Rui; Yi, Danhui; Rao, Jun; Gao, Qiangguo; Yang, Shijie; Zhang, Xi

doi:10.1097/cm9.0000000000002554

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…They are characterized by a relatively indolent rate of growth and the ability to secrete a variety of peptide hormones and biogenic amines that cause various clinical symptoms. [1,2] The heterogeneity of NENs and their non-specific symptoms, as well as physicians' lack of awareness of these diseases, may lead to errors or delays in diagnosis. [3] While the incidence of NENs is rare, several worldwide studies have revealed increasing incidences, with more evident increases seen in countries such as the USA, Canada, and Norway.…”

Section: Introductionmentioning

confidence: 99%

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Zheng

Zhao

et al. 2023

Chinese Medical Journal

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Background: Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period. Methods: Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States. Results: The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas. Conclusions: The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.

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Section: Introductionmentioning

confidence: 99%

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Zheng

Zhao

et al. 2023

Chinese Medical Journal

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“…Following the original article's publication, [ 1 ] the authors declared that the affiliation of the first author Xiaoping Li was submitted incorrectly, while correct author affiliations should be as follows. The authors apologize for any inconvenience caused.…”

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confidence: 99%

Corrigendum: Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

2023

Chinese Medical Journal

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BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications imply therapies of leukemic subclonal evolution

Chai¹,

Sui²,

Tang³

et al. 2023

Theranostics

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Rationale: In the bone marrow microenvironment (BMME), mesenchymal stem/stromal cells (MSCs) control the self-renewal of both healthy and cancerous hematopoietic stem/progenitor cells (HSPCs). We previously showed that in vivo leukemia-derived MSCs change neighbor MSCs into leukemia-permissive states and boost leukemia cell proliferation, survival, and chemotherapy resistance. But the mechanisms behind how the state changes are still not fully understood. Methods: Here, we took a reverse engineering approach to determine BCR-ABL1+ leukemia cells activated transcriptional factor C/EBPβ, resulting in miR130a/b-3p production. Then, we back-tracked from clinical specimen transcriptome sequencing to cell co-culture, molecular and cellular assays, flow cytometry, single-cell transcriptome, and transcriptional regulation to determine the molecular mechanisms of BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications. Results: BCR-ABL1-driven exosome-miR130a/b-3p mediated gap-junction Cx43 (a.k.a., GJA1) BMSC intercellular communications for subclonal evolution in leukemic microenvironment by targeting BMSCs-expressed HLAs, thereby potentially maintaining BMSCs with self-renewal properties and reduced BMSC immunogenicity. The Cx43 low and miR-130a/b high subclonal MSCs subsets of differentiation state could be reversed to Cx43 high and miR-130a/b low subclones of the higher stemness state in Cx43-overexpressed subclonal MSCs. Both miR-130a and miR-130b might only inhibit Cx43 translation or degrade Cx43 proteins and did not affect Cx43 mRNA stability. The subclonal evolution was further confirmed by single-cell transcriptome profiling of MSCs, which suggested that Cx43 regulated their stemness and played normal roles in immunomodulation antigen processing. Thus, upregulated miR-130a/b promoted osteogenesis and adipogenesis from BMSCs, thereby decreasing cancer progression. Our clinical data validated that the expression of many genes in human major histocompatibility was negatively associated with the stemness of MSCs, and several immune checkpoint proteins contributing to immune escape in tumors were overexpressed after either miR-130a or miR-130b overexpression, such as CD274, LAG3, PDCD1, and TNFRSF4. Not only did immune response-related cytokine-cytokine receptor interactions and PI3K-AKT pathways, including EGR3, TNFRSF1B, but also NDRG2 leukemic-associated inflammatory factors, such as IFNB1, CXCL1, CXCL10, and CCL7 manifest upon miR-130a/b overexpression. Either BCR siRNAs or ABL1 siRNAs assay showed significantly decreased miR-130a and miR-130b expression, and chromatin immunoprecipitation sequencing confirmed that the regulation of miR-130a and miR-130b expression is BCR-ABL1-dependent. BCR-ABL1 induces miR-130a/b expression through the upregulation of transcriptional factor C/EBPβ. C/EBPβ could...

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Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

Cited by 3 publications

References 28 publications

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States

Corrigendum: Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca2+-dependent gap junction intercellular communication

BCR-ABL1-driven exosome-miR130b-3p-mediated gap-junction Cx43 MSC intercellular communications imply therapies of leukemic subclonal evolution

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