TMT-based quantitative proteomics revealed follicle-stimulating hormone (FSH)-related molecular characterizations for potentially prognostic assessment and personalized treatment of FSH-positive non-functional pituitary adenomas

Wang, Ya; Cheng, Tingting; Lu, Min-qiang; Mu, Yun; Li, Biao; Li, Xuejun; Zhan, Xianquan

doi:10.1007/s13167-019-00187-w

Cited by 21 publications

(15 citation statements)

References 74 publications

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“…5 b-c). Noticeably, we also highlighted FSTL4 , GAS2 , AIG1 , GNG2 , FSHR and SPTA1 genes, which were associated with folliculogenesis or hormone [ 42 – 47 ]. For instance, “circ 9:131264261–131268491”, which was down-regulated in the pre- vs. post-puberty groups, might interact with FSTL4 via ssc-miR-320, might interact with GAS2 via ssc-miR-582-5p, and might interact with FSHR via ssc-miR-493-3p (Additional files 9 and 10 ).…”

Section: Resultsmentioning

confidence: 99%

Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

Pan

Gong

et al. 2021

BMC Genomics

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Background In mammals, the ovary is the essential system of female reproduction for the onset of puberty, and the abnormal puberty has negative outcomes on health. CircRNA is a non-coding RNA produced by non-canonical alternative splicing (AS). Several studies have reported that circRNA is involved in the gene regulation and plays an important role in some human diseases. However, the contribution of circRNA has received little known within the onset of puberty in ovary. Results Here, the profiles of ovarian circRNAs across pre-, in- and post-pubertal stages were established by RNA-sEq. In total, 972 circRNAs were identified, including 631 stage-specific circRNAs and 8 tissue-specific circRNAs. The biological functions of parental genes of circRNAs were enriched in steroid biosynthesis, autophagy-animal, MAPK signaling pathway, progesterone-mediated oocyte maturation and ras signaling pathway. Moreover, 5 circRNAs derived from 4 puberty-related genes (ESR1, JAK2, NF1 and ARNT) were found in this study. The A3SS events were the most alternative splicing, but IR events were likely to be arose in post-pubertal ovaries. Besides, the circRNA-miRNA-gene networks were explored for 10 differentially expressed circRNAs. Furthermore, the head-to-tail exon as well as the expressions of 10 circRNAs were validated by the divergent RT-qPCR and sanger sequencing. Conclusions In summary, the profiles of ovarian circRNAs were provided during pubertal transition in gilts, and these results provided useful information for the investigation on the onset of puberty at the ovarian-circRNAs-level in mammals.

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Section: Resultsmentioning

confidence: 99%

Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

Pan

Gong

et al. 2021

BMC Genomics

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“…After that, differentially expressed genes were used to predict the circRNA-miRNA-gene regulatory network ( Figure 4 b). Noticeably, we highlight FSTL4 , TSHR , SULT1E1 , NPFFR2 , RGCC , and ADAMTS4 genes, which were associated with puberty [ 34 , 35 , 36 , 37 , 38 , 39 ] ( Supplementary Table S7 ). Interestingly, one of these differentially expressed circRNAs, “circ 11:4104218-4118265” that interacted with FSTL4 via ssc-miR-34a, was down-regulated in the pre- vs. in-puberty groups, as well as down-regulated in the pre- vs. post-puberty groups ( Supplementary Tables S6 and S7 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of Circular RNAs in Hypothalamus of Gilts during the Onset of Puberty

Pan

et al. 2021

Genes

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The disorders of puberty have shown negative outcomes on health of mammals, and the hypothalamus is thought to be the main regulator of puberty by releasing GnRH. Many studies show that the circular RNAs (circRNAs) might be implicated in the timing of puberty in mammals. However, the circRNAs in the hypothalamus of gilts have not been explored. To profile the changes and biological functions of circRNAs in the hypothalamus during the onset of puberty, RNA-seq was utilized to establish pre-, in-, and post-pubertal hypothalamic circRNAs profiles. In this study, the functions of hypothalamic circRNAs were enriched in the signaling pathway of neurotrophin, progesterone-mediated oocyte maturation, oocyte meiosis, insulin, ErbB, and mTOR, which have been highly suggested to be involved in the timing of puberty. Furthermore, 53 circRNAs were identified to be putative hypothalamus-specific expressed circRNAs, and some of them were exclusively expressed in the one of three pubertal stages. Moreover, 22 differentially expressed circRNAs were identified and chosen to construct the circRNA-miRNA-gene network. Moreover, 10 circRNAs were found to be driven by six puberty-related genes (ESR1, NF1, APP, ENPP2, ARNT, and DICER1). Subsequently, the expression changes of several circRNAs were confirmed by RT-qPCR. Collectively, the preliminary results of hypothalamic circRNAs provided useful information for the investigation of the molecular mechanism for the timing of puberty in gilts.

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“…A series of omics analyses have been performed in PAs to reach our long-term goals that clarify molecular mechanisms and discover effective biomarkers and therapeutic targets for PAs ( Zhan and Desiderio, 2010a ; Long et al, 2019 ; Cheng et al, 2019 ; Wang Y. et al, 2019 ), including NFPA quantitative transcriptomics (differentially expressed genes, DEGs) ( Moreno et al, 2005 ; Cheng et al, 2019 ), NFPA quantitative proteomics (differentially expressed proteins, DEPs) ( Moreno et al, 2005 ), NFPA proteomic mapping ( Zhan and Desiderio, 2003 ; Wang X. et al, 2015 ; Cheng et al, 2019 ), NFPA nitroproteomics ( Zhan and Desiderio, 2006 ), invasive NFPA quantitative transcriptomics ( Galland et al, 2010 ; Zhou et al, 2011 ; Wang Y. et al, 2019 ), invasive NFPA quantitative proteomics ( Zhan et al, 2014b ), control pituitary proteomic mapping ( Beranova-Giorgianni et al, 2002 ; Giorgianni et al, 2003 ; Zhao et al, 2005 ), pituitary control nitroproteomics ( Zhan and Desiderio, 2004 ; Zhan and Desiderio, 2007 ), control pituitary phosphoproteomics ( Giorgianni et al, 2004 ; Beranova-Giorgianni et al, 2006 ), PRL-secreting adenoma proteomics and transcriptomics ( Evans et al, 2008 ), and ACTH-secreting adenoma proteomics and metabolomics ( Feng et al, 2018 ). Integrative analysis of these omics data has revealed some important signaling pathway network alterations in PA pathogenesis, including mitochondrial dysfunction, oxidative stress, cell cycle dysregulation, and mitogen-activated protein kinase (MAPK) signaling pathway alteration ( Zhan and Desiderio, 2010a ; Long et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas

Zhan

Zhou

2021

Front. Pharmacol.

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Oxidative stress and oxidative damage are the common pathophysiological characteristics in pituitary adenomas (PAs), which have been confirmed with many omics studies in PA tissues and cell/animal experimental studies. Nuclear factor erythroid 2 p45-related factor 2 (Nrf2), the core of oxidative stress response, is an oxidative stress sensor. Nrf2 is synthesized and regulated by multiple factors, including Keap1, ERK1/2, ERK5, JNK1/2, p38 MAPK, PKC, PI3K/AKT, and ER stress, in the cytoplasm. Under the oxidative stress status, Nrf2 quickly translocates from cytoplasm into the nucleus and binds to antioxidant response element /electrophile responsive element to initiate the expressions of antioxidant genes, phases I and II metabolizing enzymes, phase III detoxifying genes, chaperone/stress response genes, and ubiquitination/proteasomal degradation proteins. Many Nrf2 or Keap1 inhibitors have been reported as potential anticancer agents for different cancers. However, Nrf2 inhibitors have not been studied as potential anticancer agents for PAs. We recommend the emphasis on in-depth studies of Nrf2 signaling and potential therapeutic agents targeting Nrf2 signaling pathways as new therapeutic strategies for PAs. Also, the use of Nrf2 inhibitors targeting Nrf2 signaling in combination with ERK inhibitors plus p38 activators or JNK activators targeting MAPK signaling pathways, or drugs targeting mitochondrial dysfunction pathway might produce better anti-tumor effects on PAs. This perspective article reviews the advances in oxidative stress and Nrf2-mediated oxidative stress response signaling pathways in pituitary tumorigenesis, and the potential of targeting Nrf2 signaling pathways as a new therapeutic strategy for PAs.

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TMT-based quantitative proteomics revealed follicle-stimulating hormone (FSH)-related molecular characterizations for potentially prognostic assessment and personalized treatment of FSH-positive non-functional pituitary adenomas

Cited by 21 publications

References 74 publications

Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

Ovary-derived circular RNAs profile analysis during the onset of puberty in gilts

Identification of Circular RNAs in Hypothalamus of Gilts during the Onset of Puberty

Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas

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