Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Dai, Miao; Zhu, Xiaolu; Liu, Fei; Xu, Qinyang; Ge, Qiulin; Jiang, Shu‐Heng; Yang, Xiaomei; Li, Jun; Wang, Yahui; Wu, Qingnan; Ai, Zhihong; Teng, Yincheng; Zhang, Z.

doi:10.1038/srep41404

Cited by 48 publications

(49 citation statements)

References 38 publications

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“…DHCR7 was found to be an important regulatory determinate between cholesterol and vitamin synthesis, as cholesterol is able to accelerate the proteasomal degradation of DHCR7, which can result in the accumulation of 7DHC and an increased production of vitamin D ( 126 ). DHCR24, which was also affected by modulation of HE4 levels, is another enzyme in the cholesterol biosynthesis pathway ( 127 ). It interacts physically and functionally with DHCR7 ( 128 ) and has a number of different cellular functions including anti-inflammatory and antiapoptotic functions, as well as regulation of oxidative stress and cell differentiation ( 129 ).…”

Section: Steroid Biosynthesismentioning

confidence: 99%

“…It interacts physically and functionally with DHCR7 ( 128 ) and has a number of different cellular functions including anti-inflammatory and antiapoptotic functions, as well as regulation of oxidative stress and cell differentiation ( 129 ). DHCR24 has also been proposed to be involved in tumor progression, as its deregulation has been linked to prostate, ovarian, and urothelial carcinomas ( 127 ).…”

Section: Steroid Biosynthesismentioning

confidence: 99%

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Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer

2018

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Human epididymis protein 4 (HE4) is an important clinical biomarker used for the detection of epithelial ovarian cancer (EOC). While much is known about the predictive power of HE4 clinically, less has been reported regarding its molecular role in the progression of EOC. A deeper understanding of HE4’s mechanistic functions may help contribute to the development of novel targeted therapies. Thus far, it has been difficult to recommend HE4 as a therapeutic target owing to the fact that its role in the progression of EOC has not been extensively evaluated. This review summarizes what is collectively known about HE4 signaling and how it functions to promote tumorigenesis, chemoresistance, and metastasis in EOC, with the goal of providing valuable insights that will have the potential to aide in the development of new HE4-targeted therapies.

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Section: Steroid Biosynthesismentioning

confidence: 99%

Section: Steroid Biosynthesismentioning

confidence: 99%

Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer

2018

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“…Firstly, cholesterol has been reported to play a role in the synthesis of estrogen and progesterone. 3β-Hydroxysteroid-Δ24 reductase (DHCR24), the nal enzyme in the cholesterol biosynthetic pathway, has been demonstrated to aggravate cancer invasion and progesterone resistance in EC (18). Additionally, dietary cholesterol consumption, including saturated fatty acid, unsaturated fatty acid, and cholesterol intake, in uences EC risk by regulating the production, metabolism, and excretion of endogenous hormones (6).…”

Section: Discussionmentioning

confidence: 99%

“…GO terms with Pvalue < 0.05 were selected and ranked by enrichment score (-log10 (P-value)). Among the BP terms, response to cholesterol, epithelial to mesenchymal transition, and base-excision repair have been reported to be associated with tumor (6,(18)(19)(20)(21). In MF terms, WNT-activated receptor activity and WNT-protein binding might play a role in tumors.…”

Section: Go and Kegg Pathway Analysesmentioning

confidence: 99%

Characteristics of Circular RNA Expression in Ishikawa Human Endometrial Carcinoma Cells with Progesterone Treatment

Wang¹,

Zheng²,

Cao³

et al. 2020

Preprint

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Background Progestins are commonly used as the conservative endocrine treatment of young early endometrial cancer (EC) patients. Circular RNAs (circRNAs) are new group players in multiple cellular functions. This study aims to identify the differentially expressed circular RNAs (DE-circRNAs) in endometrial cancer (EC) cells upon the progesterone treatment, aiding in the understanding of the impact of circRNAs in progestin therapy. Methods RNA-seq analysis was used to identify the DE-circRNAs between MPA-treated and -non-treated Ishikawa cell lines. Functional enrichment analysis and circRNA-miRNA interaction network analysis were applied to these DE-circRNAs, validated by qRT-PCR analyses. Moreover, shRNA knockdown was utilized to explore the circRNA function. Results A total of 87 circRNAs were differentially expressed in Ishikawa cell lines with MPA treatment compared with that of control cells (|fold change| ≥2.0, p < 0.05). Besides, these circRNAs were mainly enriched in cancer-related pathways, including response to cholesterol, epithelial to mesenchymal transition, and base-excision repair. The competing endogenous RNA (ceRNA) network showed that miR-296-3p, miR-1236-3p, and miR-144-5p were related to cancer. Furthermore, the qPCR results were coincident with the RNA-seq data. Of note, hsa_circ_0001860 was significantly induced upon MPA treatment. Knockdown of hsa_circ_0001860 can partially rescue the MPA-inhibited cell proliferation and invasion and regulate the expression of its interacting miRNAs. Conclusions This is the first time to evaluate the circRNA expression profile in progesterone treatment for EC. These circRNAs (e.g., hsa_circ_0001860) may be used as potential diagnostic biomarkers and treatment targets for the evaluation of EC progesterone treatment.

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“…Berisha et al (36) indicated that DHCR24 is one of the transcripts affected by bariatric surgery in obese DM patients, with enzyme activity being correlated with changes of body weight, fasting plasma glucose and glycosylated hemoglobin content. Although focusing on endometrial carcinoma, another study revealed that the enzyme encoded by DHCR24 was induced by insulin stimulation via signal transducer and activator of transcription 3, which sensitizes to insulin signaling (37,38). This mechanism is possibly associated with the pathology of diabetes due to its link with hyperinsulinemia (39,40).…”

Section: Discussionmentioning

confidence: 99%

High-resolution metabolomics determines the mode of onset of type 2 diabetes in a 3-year prospective cohort study

et al. 2017

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Type 2 diabetes mellitus (DM) is a progressive disease and the rate of progression from non-diabetes to DM varies considerably between individuals, ranging from a few months to many years. It is important to understand the mechanisms underlying the progression of diabetes. In the present study, a high-resolution metabolomics (HRM) analysis was performed to detect potential biomarkers and pathways regulating the mode of onset by comparing subjects who developed and did not develop type 2 DM at the second year in a 3-year prospective cohort study. Metabolic profiles correlated with progression to DM were examined. The subjects (n=98) were classified into four groups: Control (did not develop DM for 3 years), DM (diagnosed with DM at the start of the study), DM onset at the third year and DM onset at the second year. The focus was on the comparison of serum samples of the DM groups with onset at the second and third year from the first year, where these two groups had not developed DM, yet. Analyses involved sample examination using liquid chromatography-mass spectrometry-based HRM and multivariate statistical analysis of the data. Metabolic differences were identified across all analyses with the affected pathways involved in metabolism associated with steroid biosynthesis and bile acid biosynthesis. In the first year, higher levels of cholesterol {mass-to charge ratio (m/z) 369.35, (M+H-H2O)+}, 25-hydroxycholesterol [m/z 403.36, (M+H)+], 3α,7α-dihydroxy-5β-cholestane [m/z 443.33, (M+K)+], 4α-methylzymosterol-4-carboxylate [m/z 425.34, (M+H‑H2O)+], and lower levels of 24,25-dihydrolanosterol [m/z 429.40, (M+H)+] were evident in the group with DM onset at the second year compared with those in the group with DM onset at the third year. These results, with a focus on the cholesterol biosynthesis pathway, point to important aspects in the development of DM and may aid in the development of more effective means of treatment and prevention.

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Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

Cited by 48 publications

References 38 publications

Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer

Beyond the Biomarker: Understanding the Diverse Roles of Human Epididymis Protein 4 in the Pathogenesis of Epithelial Ovarian Cancer

Characteristics of Circular RNA Expression in Ishikawa Human Endometrial Carcinoma Cells with Progesterone Treatment

High-resolution metabolomics determines the mode of onset of type 2 diabetes in a 3-year prospective cohort study

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