HS6ST1 overexpressed in cancer-associated fibroblast and inhibited cholangiocarcinoma progression

Hu, Sheng; Xia, Chuqi; Zou, Hao; Ren, Wenjun; Liu, Lixin; Wang, Lianmin; Kang, Qiang; He, Kai; Wang, Tao; Zhang, Xiaowen

doi:10.1016/j.dld.2022.12.007

Cited by 2 publications

(1 citation statement)

References 44 publications

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“…A recent study has found that HS6ST1 deficiency causes self-limited premature puberty in humans, compared to other gonadotropin-releasing hormone (GnRH) deficient genes [15]. HS6ST1 is overexpressed in cancer-associated fibroblasts and inhibits cholangiocarcinoma progression [16]. Moreover, suppressing HS6ST3 inhibits breast cancer cell proliferation and development by decreasing insulin like growth factor 1 receptor (IGF1R) and activating XIAP associated factor 1 (XAF1) [17].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro

Li,

Shen,

Wan

et al. 2023

Discovery Medicine

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Background: Emerging evidence indicates the importance of heparan sulfate 6-O-sulfotransferase 2 (HS6ST2) in a number of developmental processes. Little is known regarding its biological function in regulating cervical cancer (CC) progression. In this study, we aim to explore the role of HS6ST2 in CC progression. Methods: The transcriptome sequencing data of CC tissues from three databases, GSE64217, GSE138080, and GSE63514, was examined for genes with significant changes. The expression profile for HS6ST2 within CC tissue was then assessed through fluorescence quantitative PCR and immunohistochemistry and compared to data from patients with clinicopathological features. A multivariate survival analysis was performed using the COX regression. The real-time quantitative PCR assessed the HS6ST2 expression profile within CC cellular cultures. The results of knocking down HS6ST2, considering the proliferative activity and invasiveness of CC cultures in vitro, were detected through cell viability assay, clonogenic assessment, tumorsphere formation analysis, 3D invasion experiment and transwell assay. The impact of HS6ST2 knockdown in CC proliferation was also evaluated in vivo using a nude mice model. Results: HS6ST2 was severely upregulated within CC tissues across the three explored databases (GSE64217, GSE138080, and GSE63514). Fluorescent quantitative PCR and immunohistochemistry experiments identified HS6ST2 as highly upregulated within patients CC tissues. Survival analysis taking into account the parameters of lymph node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, depth of invasion, pathological grade, and HS6ST2 expression level demonstrated that individuals with downregulated HS6ST2 exhibited considerably extended progression-free survival (PFS) and overall survival (OS) in comparison to upregulated HS6ST2 cases. According to the findings of COX univariate analysis, the parameters lymph node metastasis, FIGO stage, depth of invasion, pathological grade, and HS6ST2 expression level, all showed a statistically significant correlation with effect upon prognosis of CC patients. The FIGO stage, depth of invasion and expression level of HS6ST2 were identified as independent risk variables influencing CC case prognosis within subsequent COX multivariate analysis. Cell function experiments proved that HS6ST2 knockdown can considerably diminish the proliferative potential, stemness and invasive traits of CC cells. Tumor formation experiments in nude mice in vivo demonstrated that knocking down HS6ST2 can significantly thwart CC cellular proliferative properties within animal models. Conclusions: The clinicopathological features and the survival time of the patients significantly correlate with the level of HS6ST2 expression in CC tissue samples.

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Section: Introductionmentioning

confidence: 99%

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro

Li,

Shen,

Wan

et al. 2023

Discovery Medicine

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Proteome-wide Mendelian randomization provides novel insights into the pathogenesis and druggable targets of osteoporosis

Yan,

Huai,

Liang

et al. 2024

Front. Med.

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BackgroundWith the aging population, the prevalence and impact of osteoporosis are expected to rise, and existing anti-osteoporosis agents have limitations due to adverse events. This study aims to discover novel drug targets for osteoporosis.MethodsThe protein data were obtained from the latest proteome-wide association studies (PWAS) including 54, 219 participants. The osteoporosis data were extracted from a GWAS meta-analysis, characterized by heel bone mineral density (HBMD) comprising 426,824 individuals. Mendelian randomization (MR) was the primary approach used to establish genetic causality between specific traits. Summary-data-based MR (SMR), colocalization analysis, heterogeneity test, and external validation were applied to ensure the findings were reliable. The underlying mechanisms behind these causal associations were investigated by additional analyses. Finally, the druggability of the identified proteins was assessed.ResultsAfter Bonferroni correction, a total of 84 proteins were found to have a genetic association with osteoporosis. With strong colocalization evidence, proteins such as ACHE, HS6ST1, LRIG1, and LRRC37A2 were found to negatively influence HBMD, whereas CELSR2, CPE, FN1, FOXO1, and FSHB exhibited a positive association with HBMD. No significant heterogeneity was found. Additionally, CELSR2, FN1, FSHB, HS6ST1, LRIG1, and LRRC37A2 were replicated in the external validation. The effect of FSHB on HBMD was more pronounced in females compared to males. Interestingly, ACHE, LRIG1, FN1, and FOXO1 were observed to partially act on HBMD through BMI. Phewas analysis indicated that CPE and FOXO1 did not have genetic associations with any phenotypes other than osteoporosis. FN1 was highlighted as the most significant protein by protein-protein interaction network analysis.ConclusionIn conclusion, this study offers valuable insights into the role of specific proteins in the development of osteoporosis, and underscores potential therapeutic targets. Future studies should emphasize exploring these causal relationships and elucidating their underlying mechanisms.

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HS6ST1 overexpressed in cancer-associated fibroblast and inhibited cholangiocarcinoma progression

Cited by 2 publications

References 44 publications

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro

Downregulation of HS6ST2 Inhibits Cervical Cancer Cell Migration and Invasion in Vivo and in Vitro

Proteome-wide Mendelian randomization provides novel insights into the pathogenesis and druggable targets of osteoporosis

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