The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials

Li, Xin; Wang, Fanchen; Xu, Xiaolin; Zhang, Jinguo; Xu, Guoxiong

doi:10.3389/fcell.2021.636595

Cited by 28 publications

(19 citation statements)

References 133 publications

(159 reference statements)

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“…The interaction between miR-512-5p and STAT1 3′-UTR was proved by dual-luciferase reporter assay, which clarified that STAT1 was a direct target gene of miR-512-5p. Previous studies indicated that STAT1 was a double-edged sword in tumor progression [ 29 ]. Here the biological functions of STAT1 were explored and verified that STAT1 was an oncogene in BC.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

Huang

Zheng

et al. 2021

Cell Death Discov.

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Breast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

Huang

Zheng

et al. 2021

Cell Death Discov.

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“…At present, the standard treatment for OC is still cytoreductive surgery combined with platinum-based chemotherapy. However, resistance to cisplatin is the major obstacle of OC treatment, which is closely related to a poor prognosis ( Li X. et al, 2021 ). Therefore, a more accurate prediction of the effect of chemotherapy could reduce the financial and psychological burden of patients, and improve the overall prognosis to some extent.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Liu

Shen

et al. 2022

Front. Genet.

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Ovarian cancer (OC) is the most lethal gynecological malignancy, in which chemoresistance is a crucial factor leading to the poor prognosis. Recently, immunotherapy has brought new light for the treatment of solid tumors. Hence, as a kind of immunologically active cancer, it is reasonably necessary to explore the potential mechanism between immune characteristics and cisplatin resistance in OC. Our study focused on the important role of cisplatin resistance-related lncRNAs on mediating the OC tumor immune microenvironment (TIME) using an integrative analysis based on the Cancer Genome Atlas (TCGA) database. First, the cisplatin resistance-related differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were preliminarily screened to construct a DEL–DEM co-expression network. Next, the protein–protein interaction (PPI) network and pivot analysis were performed to reveal the relevance of these lncRNAs with tumor immune response. Second, the novel lncRNA CTD-2288O8.1 was identified as a key gene for the OC cisplatin resistance formation by qRT-PCR and survival analysis. Gain- and loss-of-function assays (Cell Counting Kit-8 (CCK-8) assay, wound-healing scratch assay, transwell assay, and colony formation assay) further verified the activity of CTD-2288O8.1 in OC progression as well. Third, gene set enrichment analysis (GSEA) was applied along with the correlation analyses of CTD-2288O8.1 with ImmuneScore, tumor-infiltrating immune cells (TICs), and immune inhibitory checkpoint molecules, illustrating that CTD-2288O8.1 was strongly associated with the TIME and has the potential to predict the effect of OC immunotherapy. In addition, basic experiments demonstrated that the expression of CTD-2288O8.1 impacted the EGFR/AKT signal pathway activity of OC tumor cells. Of greater significance, it promoted the M2 polarization of macrophage, which is a type of the most important components of the TIME in solid tumor. Taking together, our study revealed cisplatin resistance-related lncRNAs closely linked with tumor immunity in OC, underscoring the potential mechanism of the TIME in conferring cisplatin resistance, which provided the research basis for further clinical treatment. CTD-2288O8.1 was identified to mediate cisplatin resistance and affect the response of immunotherapy, which could serve as a promising biomarker for guiding clinical treatment and improving prognosis in OC.

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“…STAT1 plays a signi cant role in the progression and prognosis of various tumors such as gastric cancer, colorectal cancer, ovarian cancer and other tumors [18][19][20]. We all know that the combined of PD-1 and PD-L1 has a negative regulatory effect on the immune system in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of Immune Checkpoints in Breast Cancer Patients

Qiu¹,

Yan²,

Zhang

et al. 2021

Preprint

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Background: immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival (OS). Positive response to PD-1/PD-L1 blockades was observed in the treatment of solidtumors. Breast cancer (BC) patients are no exception. However, the efficacy of immunocheckpoint therapy in BC patients remains poor. A particularly important factor is the lack of studies on the expression patterns of immune checkpoints in BC patients. Method: in this study, the microarray dataset GSE10810 was downloaded from the Gene Expression Database Synthesis (GEO) to analyze the differential expression of BC genes and perform GO and KEGG analysis. Then, we explored theprognostic value of ICs for BC patients by analyzing RNA-seq and mutation data from 657 BC patients from theCancer Genome Atlas (TCGA) database. Next, we analyzed the differences in the expression of relevant immune checkpoints between 1085 BC patients and 291 healthy controls (HC) in the Genotype-Tissue Expression (GTEx) database. Finally, we analyzed the expression levels of IFNγ-R, PD-L1, STAT1, IDO and other genes in MCF-10A, MF-10AT, MCF-7, MDA-MB-231 cell lines.Results: It was found that increased expression of PD-1, PD-L1, STAT1, CTLA-4 was associated with poor OS in BC patients. In addition, co-expression of PD-L1 with PD-1, STAT1or CTLA-4 and co-expression of PD-1 with CTLA-4was related to poor OS. We analyzed associations between the proportionate expression of PD-L1 and PD-1, PD-L1 and STAT1, PD-1 and CTLA-4, PD-1 and LAG3, PD-L1 and CTLA-4 in BC patients, there was significance in correlation in both of the BC patients.The expression of STAT1 in BC patients was compared with that of HC, and it was found that STAT1 was highly expressed in BC patients. Conclusions: our results suggest that transcriptome-based co-expression of STAT1 and PD-L1 is a predictor for poor OS in BC patients, which might provide novel insight into designing combinational targeted therapy for BC.

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The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials

Cited by 28 publications

References 133 publications

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Expression Patterns of Immune Checkpoints in Breast Cancer Patients

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