Ferroptosis’s Role in Genitourinary System Cancer

Liu, Chaoying; Yang, Xia; Wang, Ye; Wu, Keyu; Li, Siqiang; Wang, Gailing; Li, Yun; Li, Chuan‐Feng; Wang, Mingcheng; Li, Enzhong

doi:10.32604/oncologie.2022.025705

Cited by 9 publications

(7 citation statements)

References 60 publications

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“…Sarcoglycan epsilon (SGCE) was progressively downregulated over time, following hypobaria–hypoxia exposure. Alternative splicing of SGCE exon 8 is regulated in a Sam68-dependent manner, plays a vital role in spermatogenesis and male fertility in mice, and may account for cell cycle arrest in response to hypoxia ( Paronetto et al, 2011 ; Liu et al, 2022 ).…”

Section: Resultsmentioning

confidence: 99%

Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis

Ji,

Wang,

Zhang

et al. 2023

Front. Cell Dev. Biol.

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Most mammals tolerate exposure to hypobaric hypoxia poorly as it may affect multiple regulatory mechanisms and inhibit cell proliferation, promote apoptosis, limit tissue vascularization, and disrupt the acid–base equilibrium. Here, we quantified the functional state of germ cell development and demonstrated the interaction between the germ and somatic cells via single-cell RNA sequencing (scRNA-seq). The present study elucidated the regulatory effects of hypobaric hypoxia exposure on germ cell formation and sperm differentiation by applying enrichment analysis to genomic regions. Hypobaric hypoxia downregulates the genes controlling granule secretion and organic matter biosynthesis, upregulates tektin 1 (TEKT1) and kinesin family member 2C (KIF2C), and downregulates 60S ribosomal protein 11 (RPL11) and cilia- and flagella-associated protein 206 (CFAP206). Our research indicated that prosaposin-G protein-coupled receptor 37 (PSAP-GPR37) ligands mediate the damage to supporting cells caused by hypobaric hypoxic exposure. The present work revealed that hypoxia injures peritubular myoid (PTM) cells and spermatocytes in the S phase. It also showed that elongating spermatids promote maturation toward the G2 phase and increase their functional reserve for sperm–egg binding. The results of this study provide a theoretical basis for future investigations on prophylactic and therapeutic approaches toward protecting the reproductive system against the harmful effects of hypobaric hypoxic exposure.

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Section: Resultsmentioning

confidence: 99%

Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis

Ji,

Wang,

Zhang

et al. 2023

Front. Cell Dev. Biol.

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“…MFSD9 encodes a transport protein, but its function in cancer has not been reported. Autophagy mediated by transmembrane protein TMEM164 degrades ferritin to promote ferroptosis ( Liu et al, 2022 ; Liu et al, 2023a ). These genes were closely related to PPARs and they all have critical functions in cancer progression, indicating the complex roles of PPARs in STAD.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of peroxisome proliferator-activated receptors to predict the drug resistance, immune microenvironment, and prognosis in stomach adenocarcinomas

Jia,

Li,

Wang

et al. 2024

PeerJ

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Background Peroxisome proliferator-activated receptors (PPARs) exert multiple functions in the initiation and progression of stomach adenocarcinomas (STAD). This study analyzed the relationship between PPARs and the immune status, molecular mutations, and drug therapy in STAD. Methods The expression profiles of three PPAR genes (PPARA, PPARD and PPARG) were downloaded from The Cancer Genome Atlas (TCGA) dataset to analyze their expression patterns across pan-cancer. The associations between PPARs and clinicopathologic features, prognosis, tumor microenvironment, genome mutation and drug sensitivity were also explored. Co-expression between two PPAR genes was calculated using Pearson analysis. Regulatory pathways of PPARs were scored using gene set variation analysis (GSVA) package. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Cell Counting Kit-8 (CCK-8) assay and transwell assay were conducted to analyze the expression and function of the PPAR genes in STAD cell lines (AGS and SGC7901 cells). Results PPARA, PPARD and PPARG were more abnormally expressed in STAD samples and cell lines when compared to most of 32 type cancers in TCGA. In STAD, the expression of PPARD was higher in Grade 3+4 and male patients, while that of PPARG was higher in patient with Grade 3+4 and age > 60. Patients in high-PPARA expression group tended to have longer survival time. Co-expression analysis revealed 6 genes significantly correlated with the three PPAR genes in STAD. Single-sample GSEA (ssGSEA) showed that the three PPAR genes were enriched in 23 pathways, including MITOTIC_SPINDLE, MYC_TARGETS_V1, E2F_TARGETS and were closely correlated with immune cells, including NK_cells_resting, T_cells_CD4_memory_resting, and macrophages_M0. Immune checkpoint genes (CD274, SIGLEC15) were abnormally expressed between high-PPAR expression and low-PPAR expression groups. TTN, MUC16, FAT2 and ANK3 genes had a high mutation frequency in both high-PPARA/PPARG and low-PPARA/PPARG expression group. Fourteen and two PPARA/PPARD drugs were identified to be able to effectively treat patients in high-PPARA/PPARG and low-PPARA/PPARG expression groups, respectively. We also found that the chemotherapy drug Vinorelbine was positively correlated with the three PPAR genes, showing the potential of Vinorelbine to serve as a treatment drug for STAD. Furthermore, cell experiments demonstrated that PPARG had higher expression in AGS and SGC7901 cells, and that inhibiting PPARG suppressed the viability, migration and invasion of AGS and SGC7901 cells. Conclusions The current results confirmed that the three PPAR genes (PPARA, PPARD and PPARG) affected STAD development through mediating immune microenvironment and genome mutation.

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“…Intracellular iron homeostasis is precisely regulated by the iron metabolism system, and the maintenance of intracellular iron homeostasis is essential for cell function and fate [ 6 ]. The mechanism of ferroptosis, which has been found in a variety of tumors [ 7 , 8 ] and degenerative diseases, is also shown to be significantly associated with OA progression [ 9 , 10 ]. Previous studies have found that chondrocytes have various features of ferroptosis under pathological conditions: abnormal iron metabolism, lipid peroxidation, and mitochondrial dysfunction [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Baicalin inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes by activating Nrf-2 signaling pathway

Liu,

Zhou,

Chen

et al. 2024

J Orthop Surg Res

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Background Osteoarthritis (OA) is a common degenerative disease involving articular cartilage, in which ferroptosis of chondrocytes plays an important role. Baicalin (BAI) exerts regulatory effects in a wide range of orthopedic diseases including OA, but its effect on ferroptosis of chondrocytes (CHs) is still unclear. The purpose of this study was to determine the effect of BAI on ferroptosis in human OA chondrocytes (OACs), and to explore its possible mechanism. Methods CHs were treated with IL-1β (10 ng/mL) to simulate inflammation in vitro. Immunofluorescence, quantitative RT-PCR, Western blotting and cell viability assay were performed to evaluate the impacts of BAI on Fe2+ level, mitochondrial dysfunction, ferroptosis-related proteins, oxidative stress and cytotoxicity in CHs. Additionally, siRNA was made use of to knock out nuclear factor E2-related factor 2 (Nrf2) to analyze the role played by Nrf2 in BAI-induced CH ferroptosis. Results BAI eliminated IL-1β-induced Fe2+ accumulation, changes in mitochondrial membrane potential and ferroptosis-related protein GPX4, SLC7A11, P53 and ACSL4 levels, as well as reactive oxygen species (ROS), lipid peroxidation (LPO) and malondialdehyde (MDA) accumulation in CHs. Besides, BAI reversed IL-1β-induced decrease of Collagen II and increase of MMP13 in CHs. Meanwhile, BAI attenuated IL-1β-induced CH toxicity and promoted Nrf2 antioxidant system activation. When Nrf2 was knocked down by siRNA, the effects of BAI on IL-1β-induced ferroptosis-related proteins and antioxidant stress in CHs were significantly weakened. Conclusions This study demonstrates that IL-1β can induce CH ferroptosis. BAI is able to inhibit IL-1β-induced CH ferroptosis and ECM degradation, and the specific mechanism may be that it can inhibit IL-1β-induced CH ferroptosis by activating Nrf2 antioxidant system to attenuate the accumulation of intracellular ROS and lipid ROS.

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Ferroptosis’s Role in Genitourinary System Cancer

Cited by 9 publications

References 60 publications

Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis

Cascading effects of hypobaric hypoxia on the testis: insights from a single-cell RNA sequencing analysis

Comprehensive analysis of peroxisome proliferator-activated receptors to predict the drug resistance, immune microenvironment, and prognosis in stomach adenocarcinomas

Baicalin inhibits IL-1β-induced ferroptosis in human osteoarthritis chondrocytes by activating Nrf-2 signaling pathway

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