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Open AccessJournal ArticleDOI

Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy

TLDR
MIR152 is reported as a new autophagy-regulating miRNA that plays a role in cisplatin-resistance and it is found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level.
Abstract
Cisplatin is commonly used in ovarian cancer treatment by inducing apoptosis in cancer cells as a result of lethal DNA damage. However, the intrinsic and acquired resistance to cisplatin in cancer cells remains a big challenge for improving overall survival. The cyto-protective functions of autophagy in cancer cells have been suggested as a potential mechanism for chemoresistance. Here, we reported MIR152 as a new autophagy-regulating miRNA that plays a role in cisplatin-resistance. We showed that MIR152 expression was dramatically downregulated in the cisplatin-resistant cell lines A2780/CP70, SKOV3/DDP compared with their respective parental cells, and in ovarian cancer tissues associated with cisplatin-resistance. Overexpression of MIR152 sensitized cisplatin-resistant ovarian cancer cells by reducing cisplatin-induced autophagy, enhancing cisplatin-induced apoptosis and inhibition of cell proliferation. A mouse subcutaneous xenograft tumor model using A2780/CP70 cells with overexpressing MIR152 was es...

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LncRNA HULC triggers autophagy via stabilizing Sirt1 and attenuates the chemosensitivity of HCC cells

TL;DR: The data reveals that the pathway ‘HULC/USP22/Sirt1/ protective autophagy’ attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.
Journal ArticleDOI

The interplay between exosomes and autophagy - partners in crime

TL;DR: The molecular machinery shared between exosome biogenesis and the autophagy pathway is summarized, and the coordination between these two processes in multiple contexts, including neurodegeneration and cancer is described.
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LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes.

TL;DR: It is demonstrated that PVT1 was up-regulated in gemcitabine-resistant pancreatic cancer cell lines and discovered to interact with ATG 14, thus promoting assembly of the autophagy specific complex I (PtdIns3K-C1) and ATG14-dependent class III PtdIns 3K activity.
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Autophagy-Regulating microRNAs and Cancer.

TL;DR: Study of autophagy-regulating miRNAs in cancer will allow a better understanding of malignancies and lead to the development of novel disease markers and therapeutic strategies, and discuss its implications for cancer biology and cancer treatment.
Journal ArticleDOI

Molecular regulation of autophagy machinery by mTOR-dependent and -independent pathways.

TL;DR: Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy.
References
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Journal ArticleDOI

The hallmarks of cancer.

TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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Methods in Mammalian Autophagy Research

TL;DR: Methods to monitor autophagy and to modulate autophagic activity are discussed, with a primary focus on mammalian macroautophagy.
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p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death

TL;DR: In this article, the polyubiquitin-binding protein p62/SQSTM1 has been shown to be involved in linking polyUBiquitinated protein aggregates to the autophagy machinery.
Journal ArticleDOI

Molecular mechanisms of cisplatin resistance

TL;DR: A systematic discussion of the mechanisms that account for the cisplatin-resistant phenotype of tumor cells are described and the development of chemosensitization strategies constitute a goal with important clinical implications.
Journal ArticleDOI

Role of autophagy in cancer

TL;DR: Evidence suggests that autophagy provides a protective function to limit tumour necrosis and inflammation, and to mitigate genome damage in tumour cells in response to metabolic stress.
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