miR-1258 Attenuates Tumorigenesis Through Targeting E2F1 to Inhibit PCNA and MMP2 Transcription in Glioblastoma

Qin, Hongkun; Gui, Yanping; Ma, Rong; Zhang, Heng; Guo, Yanju; Ye, Yuting; Li, Jia; Zhao, Li; Wang, Yajing

doi:10.3389/fonc.2021.671144

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…These findings reveal that targeting ferroptosis may help to develop novel therapeutic approaches to treat glioblastoma. microRNAs (miRNAs) are kinds of endogenous gene regulators through binding to the 3 ′ -untranslated region (UTR) of targeted messenger RNAs, and play critical roles in a broad range of biological processes, including ferroptosis and glioblastoma [16][17][18][19]. Wang et al previously revealed that miR-210-3p level was elevated in human glioblastoma tissues and positively correlated with the clinic stage.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma

et al. 2022

Analytical Cellular Pathology

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Objective. Glioblastoma is one of the most common malignant tumors in the brain, and these glioblastoma patients have very poor prognosis. Ferroptosis is involved in the progression of various tumors, including the glioblastoma. This study aims to determine the involvement of microRNA (miR)-147a in regulating ferroptosis of glioblastoma in vitro. Methods. Human glioblastoma cell lines were transfected with the inhibitor, mimic and matched negative controls of miR-147a in the presence or absence of ferroptotic inducers. To knock down the endogenous solute carrier family 40 member 1 (SLC40A1), cells were transfected with the small interfering RNA against SLC40A1. In addition, cells with or without the miR-147a mimic treatment were also incubated with temozolomide (TMZ) to investigate whether miR-147a overexpression could sensitize human glioblastoma cells to TMZ chemotherapy in vitro. Results. We found that miR-147a level was decreased in human glioblastoma tissues and cell lines and that the miR-147a mimic significantly suppressed the growth of glioblastoma cells in vitro. In addition, miR-147a expression was elevated in human glioblastoma cells upon erastin or RSL3 stimulation. Treatment with the miR-147a mimic significantly induced ferroptosis of glioblastoma cells, and the ferroptotic inhibitors could block the miR-147a mimic-mediated tumor suppression in vitro. Conversely, the miR-147a inhibitor prevented erastin- or RSL3-induced ferroptosis and increased the viability of glioblastoma cells in vitro. Mechanistically, we determined that miR-147a directly bound to the 3 ′ -untranslated region of SLC40A1 and inhibited SLC40A1-mediated iron export, thereby facilitating iron overload, lipid peroxidation, and ferroptosis. Furthermore, miR-147a mimic-treated human glioblastoma cells exhibited higher sensitivity to TMZ chemotherapy than those treated with the mimic control in vitro. Conclusion. We for the first time determine that miR-147a targets SLC40A1 to induce ferroptosis in human glioblastoma in vitro.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma

et al. 2022

Analytical Cellular Pathology

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“…The average survival time of patients with glioma is 12–15 months, the 5‐year survival rate is <5%, and the survival and prognosis of patients with GBM are worse 22 ; thus, it is important to evaluate the patient's prognosis. High expression of miR‐1258 , miR‐935 and miR‐128‐3p was associated with better overall survival (OS) in patients with GBM, 23 , 24 , 25 while low miR‐542‐3p and miR‐221/222 clusters expression was associated with better OS in patients with GBM. 26 , 27 Previous studies evaluated the effect of cell‐free circulating RNA on patients with GBM.…”

Section: Microrna Smentioning

confidence: 99%

“…MiR‐1258 can inhibit GBM cell proliferation, invasion and migration and control cell cycle by targeting transcription factor E2F1. 25 Xu et al 24 indicated that miR‐128‐3p could act on the transcription factor RUNX to enhance the sensitivity of patients with GBM to chemotherapeutic drugs and inhibit the proliferation of tumour cells. In addition, forkhead box M1 ( FOXM1 ), a member of the Forkhead Box transcription factor family, controls cell cycle processes mediated by miR‐370‐3p , which enhanced the sensitivity of patients with GBM to temozolomide.…”

Section: Microrna Smentioning

confidence: 99%

“…Transcription factors can enhance or inhibit gene expression by interacting with cis‐factors through their DNA‐binding domains. MiR‐1258 can inhibit GBM cell proliferation, invasion and migration and control cell cycle by targeting transcription factor E2F1 25 . Xu et al 24 indicated that miR‐128‐3p could act on the transcription factor RUNX to enhance the sensitivity of patients with GBM to chemotherapeutic drugs and inhibit the proliferation of tumour cells.…”

Section: Micrornasmentioning

confidence: 99%

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Systematic characterization and biological functions of non‐coding RNAs in glioblastoma

et al. 2022

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Glioblastoma multiforme (GBM) is the most malignant and aggressive type of glioma. Non‐coding RNAs (ncRNAs) are RNAs that do not encode proteins but widely exist in eukaryotic cells. The common characteristics of these RNAs are that they can all be transcribed from the genome without being translated into proteins, thus performing biological functions, particularly microRNAs (miRNAs), long non‐coding RNAs (lncRNAs) and circular RNAs. Studies have found that ncRNAs are associated with the occurrence and development of GBM, and there is a complex regulatory network among ncRNAs, which can regulate cell proliferation, migration, apoptosis and differentiation, thus provide a basis for the development of highly specific diagnostic tools and therapeutic strategies in the future. The present review aimed to comprehensively describe the biogenesis, general features and functions of regulatory ncRNAs in GBM, and to interpret the potential biological functions of these ncRNAs in GBM as well as their impact on clinical diagnosis, treatment and prognosis and discusses the potential mechanisms of these RNA subtypes leading to cancer in order to contribute to the better design of personalized GBM therapies in the future.

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“…Hu et al [57] reported that pcna expression in gastric cancer tissues was significantly upregulated compared with normal tissues, and the positive expression of pcna is a risk factor for the prognosis of patients with gastric cancer. Qin et al [58] reported that in glioblastoma (GBM), a type of microRNA (miR-1258), inhibits pcna transcription by directly targeting e2f1, which provides a new potential target for GBM therapy and other e2f1-driven cancers. According to the above reports, the up-regulated expression of pcna is related to the poor prognosis of patients with tumors, which is similar to the results we analyzed using Kaplan-Meier graphs, indicating that the increased expression of pcna is related to poor 5-and 10-year OS and RFS in sarcoma A growing body of evidence indicates that the tumor microenvironment plays an important role in the regulation of the proliferation and metastasis [59,60].…”

Section: Expression Of P16 P53 and Pcna Genes And Degree Of Immune In...mentioning

confidence: 99%

Prognostic value of p16, p53, and pcna in sarcoma and an evaluation of immune infiltration

Cai

Guo

et al. 2022

J Orthop Surg Res

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Background p16, p53, and proliferating cell nuclear antigen (pcna) genes play significant roles in many chromatin modifications and have been found to be highly expressed in a variety of tumor tissues. Therefore, they have been used as target genes for some tumor therapies. However, the differential expressions of the p16, p53, and pcna genes in human sarcomas and their effects on prognosis have not been widely reported. Methods The Oncomine dataset was used to analyze the transcription levels of p16, p53, and pcna genes, and the gene expression profile interactive analysis (GEPIA) dataset was used to analyze the differential expressions of p16, p53, and pcna. The expression levels of p16, p53, and pcna were further analyzed by Western Blotting. GEPIA and Kaplan–Meier analyses were used to analyze the prognostic value of p16, p53, and pcna. Furthermore, p16, p53, and pcna gene mutations and their association with overall survival (OS) and disease-free survival (DFS) were analyzed using cBioPortal datasets. In addition, genes co-expressed with p16, p53, and pcna were analyzed using Oncomine. The DAVID dataset was used to analyze the functional enrichment of p16, p53, pcna, and their co-expressed genes by Gene Ontology (GO) and Metascape were used to construct a network map. Finally, the immune cell infiltration of p16, p53, and pcna in patients with sarcoma was reported by Tumor Immune Estimation Resource (TIMER). Results p16, p53, and pcna were up-regulated in human sarcoma tissues and almost all sarcoma cell lines. Western Blotting showed that the expression of p16, p53, and pcna was elevated in osteosarcoma cell lines. The expression of pcna was correlated with OS, the expression of p16, p53, and pcna was correlated with relapse-free survival, and the genetic mutation of p16 was negatively correlated with OS and DFS. We also found that p16, p53, and pcna genes were positively/negatively correlated with immune cell infiltration in sarcoma. Conclusions The results of this study showed that p16, p53, and pcna can significantly affect the survival and immune status of sarcoma patients. Therefore, p16, p53, and pcna could be used as potential biomarkers of prognosis and immune infiltration in human sarcoma and provide a possible therapeutic target for sarcoma.

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miR-1258 Attenuates Tumorigenesis Through Targeting E2F1 to Inhibit PCNA and MMP2 Transcription in Glioblastoma

Cited by 9 publications

References 45 publications

MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma

MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma

Systematic characterization and biological functions of non‐coding RNAs in glioblastoma

Prognostic value of p16, p53, and pcna in sarcoma and an evaluation of immune infiltration

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