Long non-coding RNA LINC00470 in serum derived exosome: a critical regulator for proliferation and autophagy in glioma cells

Ma, Wenjia; Zhou, Yu; Liu, Min; Qin, Qiang; Cui, Yan

doi:10.1186/s12935-021-01825-y

Cited by 33 publications

(18 citation statements)

References 30 publications

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“…The results emphasized that silencing of CRNDE could impair the TMZ-induced autophagy in GBM cells through a reduction in the protein levels of LC3 II/I, Beclin 1, and Atg5, and an increase in those of p62. A recent study was reported that the lncRNA LINC00470 in GBM exosomes could inhibit autophagy and enhance the proliferation of glioma cells through binding to miR-580-3p to regulate WEE1 expression [ 39 ]. Similarly, silencing lncRNA DLEU1 could suppress TMZ-activated autophagy via regulating the expression of P62 and LC3, and promote sensitivity of glioma cells to TMZ by triggering apoptosis [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma

et al. 2021

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Background The regulatory roles of long non-coding RNA (lncRNA) CRNDE in temozolomide (TMZ) chemoresistance to glioblastoma multiforme (GBM) are still poorly understood. Therefore, the function, characteristics, and possible mechanism of CRNDE in TMZ-induced chemoresistance to GBM were explored. Methods Firstly, the expression level of CRNDE in 58 cases of glioma tissue specimens and 30 cases of normal brain tissues were tested by qRT-PCR. Meanwhile, the correlation between CRNDE expression level, the clinicopathological characteristics, and survival time of patients with glioma were analyzed. Then, the CRNDE expression in various glioma cell lines was detected, and CRNDE knockdown cell models were constructed. Subsequently, to explore the effect of CRNDE on chemosensitivity to TMZ, cell viability was detected by the CCK-8 assay and IC50 values, and cell proliferation was detected by cell clone assay and EdU assay, as well as cell survival was detected by apoptosis with flow cytometry under TMZ treatment. Further, the expression of drug-resistance protein ABCG2, autophagy related proteins, and PI3K/Akt/mTOR pathway were measured by western blot or qRT-PCR in TMZ-treated glioma cells. Finally, the mouse tumor xenograft model was established and the tumor volume and weight were measured, and ABCG2 expression was conducted by immunohistochemistry assay. Results The integrated results demonstrated lncRNA CRNDE was a poor prognosis factor for GBM patient, which was upregulated in patients who were resistant to TMZ, and closely associated with chemotherapeutic response status to TMZ treatment. Further, functional assays revealed that knockdown of CRNDE could notably reduce glioma cell viability and proliferation, and elevate cell apoptosis to enhance the chemosensitivity to TMZ in vitro and in vivo. Mechanistically, the depression of CRNDE could diminish the expression of LC3 II/I, Beclin1 and Atg5 and increase the p62 expression level to inhibit autophagy due to the activation of PI3K/Akt/mTOR pathway as well as highly correlated with ABCG2 expression. Conclusions Overall, the study provided that lncRNA CRNDE is a reliable clinical predictor of outcome and prognosis and a potential biomarker for predicting TMZ treatment response in GBM by modulating the autophagy through PI3K/Akt/mTOR pathway and ABCG2 expression which may be a novel therapeutic target for regulating TMZ sensitivity to GBM.

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Section: Discussionmentioning

confidence: 99%

Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma

et al. 2021

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“…A recent study reported that many exosomal lncRNAs could regulate tumor progression through “lncRNA–miRNA–mRNA” mode. As a dominant regulator of glioma cell autophagy, LINC00470 promoted the expression of ELFN2 through sponge of exosomal miR-101 to distract glioma cell autophagy ( 87 ). Activation of autophagy might be a clinical objective that contributes to therapeutic efficiency of immunogenic chemotherapy and/or radiation therapy.…”

Section: The Functional Role Of Exosomal Mirnas In Gliomamentioning

confidence: 99%

The Role of Exosomal miRNAs in Glioma: Biological Function and Clinical Application

et al. 2021

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Gliomas are complex and heterogeneous central nervous system tumors with poor prognosis. Despite the increasing development of aggressive combination therapies, the prognosis of glioma is generally unsatisfactory. Exosomal microRNA (miRNA) has been successfully used in other diseases as a reliable biomarker and even therapeutic target. Recent studies show that exosomal miRNA plays an important role in glioma occurrence, development, invasion, metastasis, and treatment resistance. However, the association of exosomal miRNA between glioma has not been systemically characterized. This will provide a theoretical basis for us to further explore the relationship between exosomal miRNAs and glioma and also has a positive clinical significance in the innovative diagnosis and treatment of glioma.

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“…In addition, LINC00470 was overexpressed in GDEs and associated with disease severity and postoperative survival time of glioma patients [ 23 ]. LINC00470 in GDE could competitively bind to miR-580-3p in glioma cells to modify WEE1 expression and activate the PI3K/AKT/mTOR pathway, thus suppressing autophagy and strengthening the proliferation of glioma cells [ 23 ]. LncRNA ROR1-AS1 was upregulated in glioma tissues, and the high level of ROR1-AS1 predicted a poor prognosis [ 24 ].…”

Section: Gde Ncrnas In Remodeling Glioma Behaviorsmentioning

confidence: 99%

Current landscape of tumor-derived exosomal ncRNAs in glioma progression, detection, and drug resistance

Xiao

Zhang

et al. 2021

Cell Death Dis

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Glioma is the most common and fatal tumor of the central nervous system in humans. Despite advances in surgery, radiotherapy, and chemotherapeutic agents, glioma still has a poor prognosis. The tumor microenvironment (TME) of glioma is of highly complex heterogeneity, which relies on a network-based communication between glioma cells and other stromal cell types. Exosomes are the most common type of naturally occurring extracellular vesicles, ranging in size from 40 to 160 nm, and can serve as carriers for proteins, RNAs, and other biologically active molecules. Recent evidence has shown that glioma-derived exosomes (GDEs) can be integrally detected in the local tissue and circulatory blood samples, and also can be transferred to recipient cells to mediate transmission of genetic information. Non-coding RNAs (ncRNAs) mainly including microRNA, long non-coding RNA, and circular RNA, account for a large portion of the human transcriptome. A broad range of ncRNAs encapsulated in GDEs is reported to exert regulatory functions in various pathophysiological processes of glioma. Herein, this review summarizes the latest findings on the fundamental roles of GDE ncRNAs that have been implicated in glioma behaviors, immunological regulation, diagnosis potential, and treatment resistance, as well as the current limitations and perspectives. Undoubtedly, a thorough understanding of this area will provide comprehensive insights into GDE-based clinical applications for combating gliomas.

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Long non-coding RNA LINC00470 in serum derived exosome: a critical regulator for proliferation and autophagy in glioma cells

Cited by 33 publications

References 30 publications

Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma

Knockdown lncRNA CRNDE enhances temozolomide chemosensitivity by regulating autophagy in glioblastoma

The Role of Exosomal miRNAs in Glioma: Biological Function and Clinical Application

Current landscape of tumor-derived exosomal ncRNAs in glioma progression, detection, and drug resistance

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