The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function

Ma, Xiaoli; Su, Peihong; Chen, Yin; Lin, Xiuping; Wang, Xue; Gao, Yongguang; Patil, Suryaji; War, Abdul Rouf; Qadir, Abdul; Tian, Ye; Qian, Airong

doi:10.3390/ijms21030692

Cited by 82 publications

(58 citation statements)

References 81 publications

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“…GmSRS18, as a transcription factor, was located in the cell nucleus, which showed that it functions in cell nucleus. Transcription factors were involved in the abiotic and biotic stress response in many plants [67][68][69][70][71][72]. Though there are few reports of SRS family about the abiotic stress response thus far, we demonstrated that GmSRS18 can increase the transgenic Arabidopsis sensitivity to drought and salt stresses.…”

Section: Discussionmentioning

confidence: 70%

Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean

Zhao

Song

Guo

et al. 2020

IJMS

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The plant-special SHI-RELATED SEQUENCE (SRS) family plays vital roles in various biological processes. However, the genome-wide analysis and abiotic stress-related functions of this family were less reported in soybean. In this work, 21 members of soybean SRS family were identified, which were divided into three groups (Group I, II, and III). The chromosome location and gene structure were analyzed, which indicated that the members in the same group may have similar functions. The analysis of stress-related cis-elements showed that the SRS family may be involved in abiotic stress signaling pathway. The analysis of expression patterns in various tissues demonstrated that SRS family may play crucial roles in special tissue-dependent regulatory networks. The data based on soybean RNA sequencing (RNA-seq) and quantitative Real-Time PCR (qRT-PCR) proved that SRS genes were induced by drought, NaCl, and exogenous abscisic acid (ABA). GmSRS18 significantly induced by drought and NaCl was selected for further functional verification. GmSRS18, encoding a cell nuclear protein, could negatively regulate drought and salt resistance in transgenic Arabidopsis. It can affect stress-related physiological index, including chlorophyll, proline, and relative electrolyte leakage. Additionally, it inhibited the expression levels of stress-related marker genes. Taken together, these results provide valuable information for understanding the classification of soybean SRS transcription factors and indicates that SRS plays important roles in abiotic stress responses.

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Section: Discussionmentioning

confidence: 70%

Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean

Zhao

Song

Guo

et al. 2020

IJMS

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“…Moreover, to reveal the potential functions of these target genes, we performed KEGG and GO enrichment analyses by using the tool DAVID; the target genes were enriched in FOXO signalling pathway, angiogenesis, exosome biosynthesis, cytosis, and cancer‐associated pathways ( P < 0.05) (Figure 7e–h). Notably, FoxOs (FoxO1, FoxO3, and FoxO4), which are expressed in numerous types of bone cells, have been widely shown to activate osteoblastogenesis and suppress osteoclastogenesis through several targets and pathways (Ma et al., 2020), and bone tissue regeneration is frequently linked with angiogenesis and cytosis. These results indicated that miRNAs delivered by PCa exosomes strongly and broadly affect bone homeostasis through multiple potential pathways and target genes.…”

Section: Resultsmentioning

confidence: 99%

Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1‐targeting miRNA‐92a‐1‐5p

Sui

Fan

et al. 2021

J of Extracellular Vesicle

109

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In patients with prostate cancer (PCa), bone lesions appear osteoblastic in radiographs; however, pathological fractures frequently occur in PCa patients, and bone resorption is observed in all metastatic lesions under histopathologic assessment. The mechanisms that balance the activities of osteoblasts and osteoclasts in PCa patients remain unclear. We unexpectedly discovered that PCa exosomes are critical mediators in the regulation of bone homeostasis that results in osteoclastic lesions and thereby promotes tumor growth in bone. We evaluated how exosomes derived from osteoblastic, osteoclastic, and mixed PCa cell lines affect osteoblast and osteoclast differentiation, revealing that all three types of PCa exosomes promoted osteoclastogenesis in vitro and induced osteolysis in vivo. Mechanistically, microRNAs (miRNAs) delivered by PCa exosomes were found to play several key roles in bone homeostasis. Among the delivered miRNAs, miR-92a-1-5p, the most abundant miRNA, downregulated type I collagen expression by directly targeting COLA, and thus promoting osteoclast differentiation and inhibiting osteoblastogenesis. Furthermore, PCa exosomes also markedly reduced type I collagen expression in vivo. Our findings not only offer a novel perspective on tumor bone metastasis, where-contrary to our initial hypothesis-exosomes derived from an osteoblastic tumor induce osteoclast differentiation, but also suggest potential therapeutic targets for PCa bone metastasis. K E Y WO R D S bone homeostasis, bone metastasis, COLA, exosomes, extracellular vesicles, miR-92a-1-5p, prostate cancer  INTRODUCTION Prostate cancer (PCa) is the most common cause of new cancer cases and the second leading cause of cancer-related deaths in males (Siegel et al., 2020). Bone is the most common target organ for high-grade metastatic prostate cancer (Probert et al., 2019). Bone metastasis is detected at autopsy in ∼90% of all PCa patients and remains incurable; the 5-year survival of patients is ∼30%

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“…FOXO transcription factors regulate many cellular processes, including cell survival, apoptosis, and resistance to oxidative stress. In particular, FOXO proteins regulate bone cell survival, cell cycle, proliferation, and also participate in network control among different kinds of bone cells [22]. Given that our results show that IL-6 downregulated FOXO-mediated transcription in FLSs, further research on RA pathogenesis is warranted.…”

Section: Discussionmentioning

confidence: 82%

CYR61 synthesis is Induced by Interleukin-6 and Promotes Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

Choi

Jeong

Ghang

et al. 2020

Preprint

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Background:Interleukin-6 (IL-6) is involved in fibroblast-like synoviocyte (FLS) activation and promotes pannus formation and bone and cartilage destruction in rheumatoid arthritis (RA). Cysteine-rich 61 (Cyr61) protein regulates cell proliferation, migration, and differentiation. The aim of this study was to investigate the role of Cyr61 in RA-FLS migration and invasion after IL-6 stimulation. Methods:Western blotting and reverse transcription-polymerase chain reaction were used to examine protein and mRNA levels of Cyr61, matrix metalloproteinases (MMPs), and other signalling proteins. Knockdown of gene expression was performed with siRNA, and RNA sequencing was performed for differential gene analysis. Migration and invasion were assessed by wound healing and Boyden chamber assays. Results:Cyr61 levels were elevated in FLSs from RA patients compared to those in osteoarthritis patients. Control and IL-6-treated FLSs showed differential gene expression. IL-6 stimulated protein synthesis of Cyr61, which was attenuated by the extracellular signal-related kinase 1/2 (ERK 1/2) inhibitor, PD98059, and knockdown of early growth response 3 (EGR3), but not of JUN. IL-6-induced Cyr61 protein synthesis increased expression of MMP2. Cyr61 promoted FLS migration and invasion in an autocrine manner. Knockdown of CYR61 and a neutralizing antibody attenuated Cyr61 synthesis and IL-6 induced FLS migration. Conclusions:By modulating the ERK/EGR3 pathway, IL-6 stimulated Cyr61 production and in turn increasedinvasiveness of FLS. Our data suggest that Cyr61 might be a potential target to prevent the progression of joint damage in RA.

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The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function

Cited by 82 publications

References 81 publications

Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean

Genome-Wide Analysis of the Shi-Related Sequence Family and Functional Identification of GmSRS18 Involving in Drought and Salt Stresses in Soybean

Exosomes derived from osteogenic tumor activate osteoclast differentiation and concurrently inhibit osteogenesis by transferring COL1A1‐targeting miRNA‐92a‐1‐5p

CYR61 synthesis is Induced by Interleukin-6 and Promotes Migration and Invasion of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

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