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The Interplay between Autophagy and ROS in Cancer

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A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 9292

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Special Issue Editors

Prof. Dr. Kui Wang

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Guest Editor

West China School of Basic Medical Sciences & Forensic Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
Interests: cancer biology; autophagy; oxidative stress; ROS; cancer metabolism; drug targets

Prof. Dr. Yunlong Lei

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Guest Editor

Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China
Interests: cancer; autophagy; ROS; transcription factors

Special Issue Information

Dear Colleagues,

Cancer cells are commonly characterized by oxidative stress, which is attributed to the accumulation of intracellular reactive oxygen species (ROS). The roles of ROS in cancer cells depend on their concentrations. Generally, optimal levels of ROS act as signaling molecules to promote the survival and proliferation of cancer cells. Whereas excessive ROS levels are detrimental to cells by causing biomolecular damage. Autophagy, an evolutionarily conserved catabolic process for eliminating unwanted cellular contents, is closely involved in ROS-mediated biological events in cancer cells. Similar to ROS, autophagy is also a double-edged sword in cancer. Different types of autophagy, including cytoprotective autophagy, autophagic cell death, cytostatic autophagy and autophagy arrest, have been reported. Under oxidative stress, ROS can directly or indirectly stimulate autophagy. Reciprocally, autophagy serves as a survival mechanism to scavenge excessive ROS and buffer oxidative stress. However, contradictory to the above-mentioned opinions, ROS have also been reported to inhibit, rather than induce, autophagy; and autophagy can promote, rather than suppress, ROS accumulation. The complex reciprocity in ROS and autophagy regulation in cancer seems to be highly context-dependent, and remains to be further investigated. In this issue, the roles of ROS, autophagy and their interplay mechanisms in cancer will be highlighted to enable a deeper understanding of cancer biology, which will provide novel insights into the development of ROS- or autophagy-based treatment strategies for cancer therapy.

Prof. Dr. Kui Wang
Prof. Dr. Yunlong Lei
Guest Editors

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Keywords

cancer
autophagy
ROS
oxidative stress

Published Papers (5 papers)

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Research

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17 pages, 4841 KiB

Open AccessArticle

MiR-371a-5p Positively Associates with Hepatocellular Carcinoma Malignancy but Sensitizes Cancer Cells to Oxaliplatin by Suppressing BECN1-Dependent Autophagy

by Zhenbing Lv, Xin Qiu, Pu Jin, Zhaodong Li, Yan Zhang, Lei Lv and Fangzhou Song

Life 2022, 12(10), 1651; https://doi.org/10.3390/life12101651 - 20 Oct 2022

Cited by 4 | Viewed by 1440

Abstract

Oxaliplatin (OXA)-based chemotherapy demonstrates active efficacy in advanced hepatocellular carcinoma (HCC), while resistance development limits its clinical efficacy. Thus, identifying resistance-related molecules and underlying mechanisms contributes to improving the therapeutic efficacy of HCC patients. MicroRNA-371a-5p (MiR-371a-5p) fulfills an important function in tumor progression. However, little is known about the effect of miR-371a-5p on chemotherapy response. In this study, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were used to determine the expression levels of miR-371a-5p, BECN1 and autophagy-related proteins in HCC cells, tissues and serum. The luciferase reporter assay was used to assess the directly suppressive effect of miR-371a-5p on BECN1 mRNA translation. Moreover, gain- and loss-of-function assays and rescue assays were used to evaluate the mediated effect of BECN1-dependent autophagy on the role of miR-371a-5p in the response of HCC cells to OXA. We found that miR-371a-5p was significantly up-regulated in HCC tissues and serum from patients, whereas BECN1 protein was down-regulated in HCC tissues compared to the corresponding controls. We also found that there was a negative correlation between the two molecules in HCC tissues. In addition, we found that miR-371a-5p expression was positively associated with malignant characteristics of HCC and BECN1 protein expression is negatively associated. Contrary to this, we found that miR-371a-5p enhances and BECN1 attenuates the response of HCC cells to OXA. Importantly, the enhanced effect of miR-371a-5p on the response of HCC cells to OXA could be reduced by re-expression of non-targetable BECN1, and then the reduced effect was restored following bafilomycin A treatment. Taken together, we identified a dual role of miR-371a-5p in HCC malignant characteristics and the response of HCC cells to oxaliplatin. Importantly, we reveal that miR-371a-5p enhances oxaliplatin response by target suppression of BECN1-dependent autophagy. Full article

(This article belongs to the Special Issue The Interplay between Autophagy and ROS in Cancer)

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15 pages, 3160 KiB

Open AccessArticle

MED16 Promotes Tumour Progression and Tamoxifen Sensitivity by Modulating Autophagy through the mTOR Signalling Pathway in ER-Positive Breast Cancer

by Han Li, Kang Li, Dan Shu, Meiying Shen, Zhaofu Tan, Wenjie Zhang, Dongyao Pu, Wenhao Tan, Zhenrong Tang, Aishun Jin and Shengchun Liu

Life 2022, 12(10), 1461; https://doi.org/10.3390/life12101461 - 20 Sep 2022

Cited by 2 | Viewed by 1692

Abstract

Recent studies have shown that the mediator complex (MED) plays a vital role in tumorigenesis and development, but the role of MED16 (mediator complex subunit 16) in breast cancer (BC) is not clear. Increasing evidence has shown that the mTOR pathway is important for tumour progression and therapy. In this study, we demonstrated that the mTOR signalling pathway is regulated by the expression level of MED16 in ER+ breast cancer. With the analysis of bioinformatics data and clinical specimens, we revealed an elevated expression of MED16 in luminal subtype tumours. We found that MED16 knockdown significantly inhibited cell proliferation and promoted G1 phase cell cycle arrest in ER+ BC cell lines. Downregulation of MED16 markedly reduced the sensitivity of ER+ BC cells to tamoxifen and increased the stemness and autophagy of ER+ BC cells. Bioinformatic analysis of similar genes to MED16 were mainly enriched in autophagy, endocrine therapy and mTOR signalling pathways, and the inhibition of mTOR-mediated autophagy restored sensitivity to tamoxifen by MED16 downregulation in ER+ BC cells. These results suggest an important role of MED16 in the regulation of tamoxifen sensitivity in ER+ BC cells, crosstalk between the mTOR signalling pathway-induced autophagy, and together, with the exploration of tamoxifen resistance, may indicate a new therapy option for endocrine therapy-resistant patients. Full article

(This article belongs to the Special Issue The Interplay between Autophagy and ROS in Cancer)

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11 pages, 2659 KiB

Open AccessArticle

MPP7 as a Novel Biomarker of Esophageal Cancer: MPP7 Knockdown Inhibits Esophageal Cancer Cell Migration and Invasion

by Zhaodong Li, Yongyao Tang, Jing Cai, Shunlong Wu and Fangzhou Song

Life 2022, 12(9), 1381; https://doi.org/10.3390/life12091381 - 5 Sep 2022

Cited by 2 | Viewed by 1549

Abstract

MAGUK p55 scaffold protein 7 (MPP7) is a member of the stardust family of membrane-associated guanosine kinase protein P55 and plays a role in the establishment of epithelial cell polarity. However, its potential implication in human esophageal cancer is unclear. In this study, we investigated the expression profile of MPP7 and its functional impact on esophagus cancer. Expression analyses of immunohistochemical microarrays with survival and prognostic information of 103 patients with esophageal cancer demonstrated that MPP7 was overexpressed in 52 patients, who showed poor survival rates. The transcriptional expression of MPP7 in esophageal cancer in TCGA database increased successively from normal epithelial, to esophageal adenocarcinoma, to esophageal squamous cell carcinoma. Transcriptome sequencing after MPP7 knockdown in esophageal carcinoma cells showed that wound-healing-associated proteins were down-regulated, and the TGF-β pathway was one of the important signaling pathways. A loss-of-function study showed that the knockdown of MPP7 inhibited cell migration and invasion. These results could be verified in a model of tumor cells injected into the tail vein and subcutaneous tumor of nude mice. Herein, our results indicated that MPP7 could have an oncogenic role in human esophagus cancer, thus demonstrating its potential as a novel biomarker for the diagnosis and/or treatment of esophagus cancer. Full article

(This article belongs to the Special Issue The Interplay between Autophagy and ROS in Cancer)

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15 pages, 3326 KiB

Open AccessArticle

Dihydroartemisinin Reduces Irradiation-Induced Mitophagy and Radioresistance in Lung Cancer A549 Cells via CIRBP Inhibition

by Shunlong Wu, Zhaodong Li, Haiyu Li and Kui Liao

Life 2022, 12(8), 1129; https://doi.org/10.3390/life12081129 - 27 Jul 2022

Cited by 6 | Viewed by 2072

Abstract

Radiotherapy is a major therapeutic strategy for lung cancer, and radiation resistance (radioresistance) is an important cause of residual and recurring cancer after treatment. However, the mechanism of radioresistance remains unclear. Mitochondrial autophagy (mitophagy), an important selective autophagy, plays an important role in maintaining cell homeostasis and affects the response to therapy. Recent studies have shown that dihydroartemisinin (DHA), a derivative of artemisinin, can increase the sensitivity to treatment in multiple types of cancer, including lung cancer. The purpose of this study was to elucidate the function and molecular mechanisms of DHA-regulating mitophagy and DHA-reducing radioresistance in lung cancer A549 cells. We first constructed the radioresistant lung cancer A549 cells model (A549R) through fractional radiation, then elucidated the function and mechanism of DHA-regulating mitophagy to reduce the radioresistance of lung cancer by genomic, proteomic, and bioinformatic methods. The results showed that fractional radiation can significantly induce radioresistance and mitophagy in A549 cells, DHA can reduce mitophagy and radioresistance, and the inhibition of mitophagy can reduce radioresistance. Protein chip assay and bioinformatics analysis showed the following: Cold-Inducible RNA Binding Protein (CIRBP) might be a potential target of DHA-regulating mitophagy; CIRBP is highly expressed in A549R cells; the knockdown of CIRBP increases the effect of DHA, reduces mitophagy and radioresistance, and inhibits the mitophagy-related PINK1/Parkin pathway. In conclusion, we believe that DHA reduces radiation-induced mitophagy and radioresistance of lung cancer A549 cells via CIRBP inhibition. Full article

(This article belongs to the Special Issue The Interplay between Autophagy and ROS in Cancer)

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Review

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21 pages, 1676 KiB

Open AccessReview

Redox Regulation of Autophagy in Cancer: Mechanism, Prevention and Therapy

by Jingqiu He, Lixia Dong, Li Luo and Kui Wang

Life 2023, 13(1), 98; https://doi.org/10.3390/life13010098 - 29 Dec 2022

Cited by 8 | Viewed by 1856

Abstract

Reactive oxygen species (ROS), products of normal cellular metabolism, play an important role in signal transduction. Autophagy is an intracellular degradation process in response to various stress conditions, such as nutritional deprivation, organelle damage and accumulation of abnormal proteins. ROS and autophagy both exhibit double-edged sword roles in the occurrence and development of cancer. Studies have shown that oxidative stress, as the converging point of these stimuli, is involved in the mechanical regulation of autophagy process. The regulation of ROS on autophagy can be roughly divided into indirect and direct methods. The indirect regulation of autophagy by ROS includes post-transcriptional and transcriptional modulation. ROS-mediated post-transcriptional regulation of autophagy includes the post-translational modifications and protein interactions of AMPK, Beclin 1, PI3K and other molecules, while transcriptional regulation mainly focuses on p62/Keap1/Nrf2 pathway. Notably, ROS can directly oxidize key autophagy proteins, such as ATG4 and p62, leading to the inhibition of autophagy pathway. In this review, we will elaborate the molecular mechanisms of redox regulation of autophagy in cancer, and discuss ROS- and autophagy-based therapeutic strategies for cancer treatment. Full article

(This article belongs to the Special Issue The Interplay between Autophagy and ROS in Cancer)

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