Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling

Liang, Zongwen; Wu, Qiong; Wang, Honglin; Tan, Jiahuan; Wang, Han; Gou, Yanling; Cao, Yingying; Li, Zhi; Zhang, Zongfeng

doi:10.1038/s41420-022-00975-w

Cited by 43 publications

(29 citation statements)

References 30 publications

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“…The diagnosis of endometriosis was established through laparoscopy and histological confirmation. As controls, endometrial tissue samples were obtained from cycling women, age-and menstrual phase-matched (in frequency) with those endometrioses who underwent hysterectomy with uterine leiomyoma or grade II-III cervical intraepithelial neoplasia (CIN), and without clinical indication or history of endometriosis or adenomyosis [32,33]. The tissue sampled in our study was approved by the Human Assurance Committee of Affiliated Hospital of Weifang Medical University (Ethics number 2021YX028).…”

Section: Tissue Samples and Endometriosis Mouse Modelmentioning

confidence: 99%

Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis

Lü

Qiao

et al. 2022

Cell Death Dis

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Endometriosis (EM) is one of the vanquished wonted causes of chronic pelvic sting in women and is closely associated with infertility. The long-term, complex, systemic, and post-treatment recurrence of EM wreaks havoc on women's quality of life. Extensive metabolic reprogramming (aerobic glycolysis, glucose overweening intake, and high lactate production) and cancer-like changes have been found in EM, which bears striking similarities to tumorigenesis. The key glycolysis regulator PFKFB4 is overexpressed in EM. However, the mechanism of PFKFB4 in EM remains unknown. We found that PFKFB4 was upregulated and was closely related to the progression of EM. We identified focus PIM2 as a new pioneering adjoin protein of PFKFB4. Vigorous biochemical methods were used to confirm that PIM2 phosphorylated site Thr140 of PFKFB4. PIM2 also could enhance PFKFB4 protein expression through the ubiquitin-proteasome pathway. Moreover, PIM2 expression was really corresponding prevalent with PFKFB4 in endometriosis in vivo. Importantly, phosphorylation of PFKFB4 on Thr140 by PIM2 promoted EM glycolysis and cell growth. Our study demonstrates that PIM2 mediates PFKFB4 Thr140 phosphorylation thus regulating glycolysis and EM progression. We illustrated a new mechanism that PIM2 simulated a central upstream partnership in the regulation of PFKFB4, and reveal a novel means of PIM2-PFKFB4 setting EM growth. Our research provided new theoretical support for further clarifying the reprogramming of EM glucose metabolism, and provided new clues for exploring non-contraceptive treatments for EM.

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Section: Tissue Samples and Endometriosis Mouse Modelmentioning

confidence: 99%

Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis

Lü

Qiao

et al. 2022

Cell Death Dis

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“…We found MALAT1 was positively associated with exosome characteristics, and others found that exosome-mediated intercellular communication allowed the transfer of MALAT1 as a lncRNA to play a regulatory role ( 54 , 55 ). In contrast, MALAT1 was negatively associated with ferroptosis signature, and one study reported that silencing MALAT1 induced ferroptosis ( 56 ), reflecting the possibility that MALAT1 may also contribute to the development of HCC by inhibiting ferroptosis. TIL prediction analysis showed that high MALAT1 expression was associated with several immunosuppressive signatures, such as reduced macrophage infiltration and increased fibroblast infiltration.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation

Liao¹,

Chen²,

Luo³

et al. 2023

Pathol. Oncol. Res.

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Background: This study aimed to explore the relationship between MALAT1 and the prognosis of patients with hepatocellular carcinoma (HCC).Methods: We constructed a MALAT1 protein-protein interaction network using the STRING database and a network of competing endogenous RNAs (ceRNAs) using the StarBase database. Using data from the GEPIA2 database, we studied the association between genes in these networks and survival of patients with HCC. The potential mechanisms underlying the relationship between MALAT1 and HCC prognosis were studied using combined data from RNA sequencing, DNA methylation, and somatic mutation data from The Cancer Genome Atlas (TCGA) liver cancer cohort. Tumor tissues and 19 paired adjacent non-tumor tissues (PANTs) from HCC patients who underwent radical resection were analyzed for MALAT1 mRNA levels using real-time PCR, and associations of MALAT1 expression with clinicopathological features or prognosis of patients were analyzed using log-rank test and Gehan-Breslow-Wilcoxon test.Results: Five interacting proteins and five target genes of MALAT1 in the ceRNA network significantly correlated with poor survival of patients with HCC (p < 0.05). High MALAT1 expression was associated with mutations in two genes leading to poor prognosis and may upregulate some prognostic risk genes through methylation. MALAT1 was significantly co-expressed with various signatures of genes involved in HCC progression, including the cell cycle, DNA damage repair, mismatch repair, homologous recombination, molecular cancer m6A, exosome, ferroptosis, infiltration of lymphocyte (p < 0.05). The expression of MALAT1 was markedly upregulated in HCC tissues compared with PANTs. In Kaplan-Meier analysis, patients with high MALAT1 expression had significantly shorter progression-free survival (PFS) (p = 0.033) and overall survival (OS) (p = 0.023) than those with low MALAT1 expression. Median PFS was 19.2 months for patients with high MALAT1 expression and 52.8 months for patients with low expression, while the corresponding median OS was 40.5 and 78.3 months. In subgroup analysis of patients with vascular invasion, cirrhosis, and HBsAg positive or AFP positive, MALAT1 overexpression was significantly associated with shorter PFS and OS. Models for predicting PFS and OS constructed based on MALAT1 expression and clinicopathological features had moderate predictive power, with areas under the receiver operating characteristic curves of 0.661–0.731. Additionally, MALAT1 expression level was significantly associated with liver cirrhosis, vascular invasion, and tumor capsular infiltration (p < 0.05 for all).Conclusion:MALAT1 is overexpressed in HCC, and higher expression is associated with worse prognosis. MALAT1 mRNA level may serve as a prognostic marker for patients with HCC after hepatectomy.

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“…To systemically explore the potential ceRNA mechanisms between these differentially expressed lncRNAs and Becn1, miRNAs bound with Becn1 and lncRNAs bound with miRNAs were predicted respectively by Starbase database, then the predicted lncRNAs were intersected with the differentially up-regulated lncRNAs to obtain lncRNA/miRNA/mRNA ceRNA network, the results showed there were Rian/mmu-miR-145a-5p/Becn1, Tug1/mmu-miR-145a-5p/Becn1, Malat1/mmu-miR-30e-5p/Becn1 and H19/mmu-miR-299a-3p/Becn1 axes respectively. There have been reported that lncRNA Rian, lncRNA Tug1, lncRNA Malat1 and lncRNA H19 all serve as ceRNA involved in multiple biological process, such as apoptosis ( Wu et al, 2020 ; Yao et al, 2020 ), ferroptosis ( Liang et al, 2022 ; Zhang et al, 2022 ) and pyroptosis ( Sun, Mao & Ji, 2021 ; Kang et al, 2022 ). Zhang and He reported that lncRNA Malat1/mmu-miR-30a/Becn1 was involved in myocardial infarction ( Zhang & He, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury

et al. 2023

PeerJ

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Background Ferroptosis and long-noncoding RNAs (lncRNAs) play crucial roles in doxorubicin (DOX)-induced myocardial injury (DIMI). Nevertheless, there is no research to construct competing endogenous RNAs (ceRNAs) network between lncRNAs and ferroptosis-related key gene. So our research was designed to screen ferroptosis-related genes from differentially expressed mRNAs in DIMI and construct lncRNAs regulated ferroptosis-related key gene ceRNAs network. Methods The male mice were injected with DOX intraperitoneally to induce myocardial injury, myocardial injury was evaluated by hematoxylin and eosin (HE) staining, and ferroptosis-related protein-glutathione peroxidase 4 (GPx4) protein expression was detected. The differentially expressed lncRNAs and mRNAs were detected by microarray, and the ferroptosis-related genes were screened to construct a protein-protein associations (PPA) network, the highest maximal clique centrality (MCC) score gene were identified by Cytoscape software, miRNAs bound to key genes and lncRNAs bound to miRNAs were predicted; then, the obtained lncRNAs were intersected with differentially expressed lncRNAs detected by microarray. Finally, the lncRNA/miRNA/mRNA ceRNA network of the highest MCC score gene regulating ferroptosis in DIMI was constructed. The expressions of the key components in ceRNA network were detected by qRT-PCR. Results Compared with the control group, in the DOX group, myocardial enzymes and HE staining showed that myocardium structure was changed, and GPx4 protein expression was decreased. The differentially expressed 10,265 lncRNAs and 6,610 mRNAs in the DOX group were detected via microarray. Among them, 114 ferroptosis-related genes were obtained to construct PPA networks, and Becn1 was identified as the key gene. Finally, the ceRNA network including Becn1, three miRNAs and four lncRNAs was constructed by predicting data of the Starbase database. The relative expressions of these components in ceRNA net were up-regulated and consistent with microarray results. Conclusions Based on the microarray detection results and bioinformatics analysis, we screened ferroptosis-related gene Becn1 and constructed the lncRNA/miRNA/mRNA ceRNA network of regulated ferroptosis in DIMI.

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Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling

Cited by 43 publications

References 30 publications

Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis

Phosphorylation of PFKFB4 by PIM2 promotes anaerobic glycolysis and cell proliferation in endometriosis

Prognostic value of long non-coding RNA MALAT1 in hepatocellular carcinoma: A study based on multi-omics analysis and RT-PCR validation

Construction of a ceRNA network of regulated ferroptosis in doxorubicin-induced myocardial injury

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