SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway

Chen, Mo; Zeng, Jia; Chen, Shuyi; Li, Jiajia; Wu, Huihui; Dong, Xuhui; Liu, Yuan; Zhi, Xiuling; Yao, Liangqing

doi:10.18632/aging.103303

Cited by 25 publications

(20 citation statements)

References 39 publications

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“…In the context of ovarian cancer metastasis and cell migration, little is known about the role of βII spectrin. A recent study indicated that βII spectrin mediates the inhibition of JAK/STAT signaling pathway through suppressor of cytokine signaling 3 (SOCS3), thereby inhibiting cell growth and migration in epithelial ovarian cancer 105 . Additionally, βII spectrin has been shown to be involved in the resistance of serous ovarian cancer to cisplatin treatment 106 .…”

Section: The Involvement Of βIi Spectrin In Cancermentioning

confidence: 99%

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Yang¹,

Yang²,

Sun³

et al. 2021

Int. J. Biol. Sci.

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βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

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Section: The Involvement Of βIi Spectrin In Cancermentioning

confidence: 99%

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Yang¹,

Yang²,

Sun³

et al. 2021

Int. J. Biol. Sci.

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show abstract

“…For instance, Zhi et al (2015) demonstrated that SPTBN1 inhibited the development of hepatocellular carcinoma via modulating the expression of Wnt inhibitor Kallistatin to intervene in the Wnt signaling pathway. Chen et al (2020) reported that SPTBN1 can prevent the progression of epithelial ovarian cancer through the SOCS3-mediated blockade of the JAK/STAT3 signaling pathway. Besides, SPTBN1 has been implicated in the development of osteoporotic fracture and bone mineral density (BMD).…”

Section: Introductionmentioning

confidence: 99%

SPTBN1 Prevents Primary Osteoporosis by Modulating Osteoblasts Proliferation and Differentiation and Blood Vessels Formation in Bone

Yang

et al. 2021

Front. Cell Dev. Biol.

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Osteoporosis is a common systemic skeletal disorder that leads to increased bone fragility and increased risk of fracture. Although βII-Spectrin (SPTBN1) has been reported to be involved in the development of various human cancers, the function and underlying molecular mechanisms of SPTBN1 in primary osteoporosis remain unclear. In this study, we first established a primary osteoporosis mouse model of senile osteoporosis and postmenopausal osteoporosis. The results showed that the expression of SPTBN1 was significantly downregulated in primary osteoporosis mice model compared with the control group. Furthermore, silencing of SPTBN1 led to a decrease in bone density, a small number of trabecular bones, wider gap, decreased blood volume fraction and number of blood vessels, as well as downregulation of runt-related transcription factor 2 (Runx2), Osterix (Osx), Osteocalcin (Ocn), and vascular endothelial growth factor (VEGF) in primary osteoporosis mice model compared with the control group. Besides, the silencing of SPTBN1 inhibited the growth and induced apoptosis of mouse pre-osteoblast MC3T3-E1 cells compared with the negative control group. Moreover, the silencing of SPTBN1 significantly increased the expression of TGF-β, Cxcl9, and the phosphorylation level STAT1 and Smad3 in MC3T3-E1 cells compared with the control group. As expected, overexpression of SPTBN1 reversed the effect of SPTBN1 silencing in the progression of primary osteoporosis both in vitro and in vivo. Taken together, these results suggested that SPTBN1 suppressed primary osteoporosis by facilitating the proliferation, differentiation, and inhibition of apoptosis in osteoblasts via the TGF-β/Smad3 and STAT1/Cxcl9 pathways. Besides, overexpression of SPTBN1 promoted the formation of blood vessels in bone by regulating the expression of VEGF. This study, therefore, provided SPTBN1 as a novel therapeutic target for osteoporosis.

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“…Previous studies demonstrated that SOCS family members were abnormally expressed in various cancers and may serve as prognostic biomarkers. Besides, many studies have shown that SCOS expression was dysregulated in various cancers and played an important role in tumor development and progression [8][9][10]. Previous research suggests that SOCS family genes can be regarded as prognostic markers of breast cancer and gastric cancer patients [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Expression Status and Prognostic Values of SOCS Family Genes in Non-small Cell Lung Cancer

Zhang¹,

Sun²,

Bao³

2021

Preprint

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Backgroud:Suppressors of cytokine signaling (SOCS) family play important roles in the development of cancers by inhibiting the transmission of the Janus kinases–signal transducers and activators of transcription (JAK-STAT) signaling pathway. However, the expression patterns and prognostic value of SOCS family genes in non-small cell lung cancer (NSCLC) remains unclear. Methods: The SOCS family genes expression profiles were explored using ONCOMINE and GEPIA online tools. The mutation and copy number alterations of SOCS family genes in NSCLC were assessed by cBioportal for Cancer Genomics. The methylation status of SOCS family members were analyzed through MEXPRESS and UCSC Xena website. The prognostic values of SOCS family genes in NSCLC were explored through Kaplan-Meier Plotter database. Results: The expression levels of SOCS2, SOCS3, and cytokine-inducible SH2-containing protein (CIS/CISH) were significantly reduced in NSCLC tissues compared to normal lung tissues. The aberrant DNA methylation of SOCS family genes were frequent in NSCLC. CISH methylation was negatively correlated with gene expression in NSCLC. The Kaplan-Meier Plotter analysis demonstrated high expression of SOCS1 may be a predictor of poor prognosis in lung adenocarcinoma(LUAD) but served as a favorable prognostic marker of lung squamous cell carcinoma. The high expression levels of SOCS2 and SOCS4-7 were significantly correlated with better overall survival (OS) in LUAD but not in lung squamous carcinoma (LUSC) patients. Conclusions:Our findings indicated that the aberrant gene expression and DNA methylation of SOCS family members are common in NSCLC and contribute to tumorigenesis. SOCS family genes may serve as therapeutic targets and prognostic biomarkers for NSCLC patients

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SPTBN1 suppresses the progression of epithelial ovarian cancer via SOCS3-mediated blockade of the JAK/STAT3 signaling pathway

Cited by 25 publications

References 39 publications

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

SPTBN1 Prevents Primary Osteoporosis by Modulating Osteoblasts Proliferation and Differentiation and Blood Vessels Formation in Bone

Expression Status and Prognostic Values of SOCS Family Genes in Non-small Cell Lung Cancer

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