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1
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Qin P, Li Q, Zu Q, Dong R, Qi Y. Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy. Front Oncol 2024; 14:1379698. [PMID: 38628670 PMCID: PMC11019012 DOI: 10.3389/fonc.2024.1379698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/18/2024] [Indexed: 04/19/2024] Open
Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. The roles of autophagy and apoptosis in NSCLC present a dual and intricate nature. Additionally, autophagy and apoptosis interconnect through diverse crosstalk molecules. Owing to their multitargeting nature, safety, and efficacy, natural products have emerged as principal sources for NSCLC therapeutic candidates. This review begins with an exploration of the mechanisms of autophagy and apoptosis, proceeds to examine the crosstalk molecules between these processes, and outlines their implications and interactions in NSCLC. Finally, the paper reviews natural products that have been intensively studied against NSCLC targeting autophagy and apoptosis, and summarizes in detail the four most retrieved representative drugs. This paper clarifies good therapeutic effects of natural products in NSCLC by targeting autophagy and apoptosis and aims to promote greater consideration by researchers of natural products as candidates for anti-NSCLC drug discovery.
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Affiliation(s)
- Peiyi Qin
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Qingchen Li
- Department of Orthopedics, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qi Zu
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Ruxue Dong
- Shandong College of Traditional Chinese Medicine, Yantai, Shandong, China
| | - Yuanfu Qi
- Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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2
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Wang HX, Zhao ZP, Du XY, Peng SL, Xu HY, Tang W, Yang L. SLFN11 promotes clear cell renal cell carcinoma progression via the PI3K/AKT signaling pathway. Med Oncol 2024; 41:54. [PMID: 38206539 DOI: 10.1007/s12032-023-02262-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/18/2023] [Indexed: 01/12/2024]
Abstract
SLFN11 is abnormally expressed and associated with survival outcomes in various human cancers. However, the role of SLFN11 in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the clinical value and potential functions of SLFN11 in ccRCC. Comprehensive bioinformatics analyses were performed using online databases. Quantitative real-time PCR (qPCR) and western blotting were used to validate the expression data. CCK8, flow cytometry analysis, and EdU staining were performed to determine the level of cell proliferation. Flow cytometry analysis was also used to detect cell apoptosis. Wound-healing assay and Transwell assays were performed to assess cell migration and invasion capability, respectively. SLFN11 was overexpressed and was an independent prognostic factor in ccRCC. SLFN11 knockdown inhibited cell proliferation, migration, and invasion and promoted apoptosis. Functional and pathway enrichment analyses suggested that SLFN11 may have an impact on tumorigenesis in ccRCC through regulation of the inflammatory response, the PI3K/AKT signaling pathway and other effectors. Furthermore, SLFN11 knockdown inhibited the phosphorylation of the PI3K/AKT signaling pathway and could be activated by 740 Y-P. Finally, we demonstrated that miR-183 may specifically target SLFN11, and miR-183 expression was correlated with predicted survival. SLFN11 may play a critical role in ccRCC progression and may serve as a novel prognostic biomarker in ccRCC.
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Affiliation(s)
- He-Xi Wang
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Zhi-Peng Zhao
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Xiao-Yi Du
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Sen-Lin Peng
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Hao-Yu Xu
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China
| | - Wei Tang
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
| | - Lei Yang
- Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
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3
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Rashid S, Dimitriadi M. Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches. Front Cell Neurosci 2024; 17:1307636. [PMID: 38259504 PMCID: PMC10801191 DOI: 10.3389/fncel.2023.1307636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 12/14/2023] [Indexed: 01/24/2024] Open
Abstract
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by the depletion of the ubiquitously expressed survival motor neuron (SMN) protein. While the genetic cause of SMA has been well documented, the exact mechanism(s) by which SMN depletion results in disease progression remain elusive. A wide body of evidence has highlighted the involvement and dysregulation of autophagy in SMA. Autophagy is a highly conserved lysosomal degradation process which is necessary for cellular homeostasis; defects in the autophagic machinery have been linked with a wide range of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson's disease. The pathway is particularly known to prevent neurodegeneration and has been suggested to act as a neuroprotective factor, thus presenting an attractive target for novel therapies for SMA patients. In this review, (a) we provide for the first time a comprehensive summary of the perturbations in the autophagic networks that characterize SMA development, (b) highlight the autophagic regulators which may play a key role in SMA pathogenesis and (c) propose decreased autophagic flux as the causative agent underlying the autophagic dysregulation observed in these patients.
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Affiliation(s)
| | - Maria Dimitriadi
- School of Life and Medical Science, University of Hertfordshire, Hatfield, United Kingdom
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4
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Mu YR, Zou SY, Li M, Ding YY, Huang X, He ZH, Kong WJ. Role and mechanism of FOXG1-related epigenetic modifications in cisplatin-induced hair cell damage. Front Mol Neurosci 2023; 16:1064579. [PMID: 37181652 PMCID: PMC10169754 DOI: 10.3389/fnmol.2023.1064579] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Accepted: 04/11/2023] [Indexed: 05/16/2023] Open
Abstract
Cisplatin is widely used in clinical tumor chemotherapy but has severe ototoxic side effects, including tinnitus and hearing damage. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. In this study, we used CBA/CaJ mice to establish an ototoxicity model of cisplatin-induced hair cell loss, and our results showed that cisplatin treatment could reduce FOXG1 expression and autophagy levels. Additionally, H3K9me2 levels increased in cochlear hair cells after cisplatin administration. Reduced FOXG1 expression caused decreased microRNA (miRNA) expression and autophagy levels, leading to reactive oxygen species (ROS) accumulation and cochlear hair cell death. Inhibiting miRNA expression decreased the autophagy levels of OC-1 cells and significantly increased cellular ROS levels and the apoptosis ratio in vitro. In vitro, overexpression of FOXG1 and its target miRNAs could rescue the cisplatin-induced decrease in autophagy, thereby reducing apoptosis. BIX01294 is an inhibitor of G9a, the enzyme in charge of H3K9me2, and can reduce hair cell damage and rescue the hearing loss caused by cisplatin in vivo. This study demonstrates that FOXG1-related epigenetics plays a role in cisplatin-induced ototoxicity through the autophagy pathway, providing new ideas and intervention targets for treating ototoxicity.
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Affiliation(s)
- Yu-rong Mu
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sheng-yu Zou
- Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ming Li
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan-yan Ding
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Huang
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zu-hong He
- Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei-jia Kong
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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5
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Wang Z, Liu J, Xie J, Yuan X, Wang B, Shen W, Zhang Y. Regulation of autophagy by non-coding RNAs in gastric cancer. Front Oncol 2022; 12:947332. [PMID: 36353541 PMCID: PMC9637602 DOI: 10.3389/fonc.2022.947332] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 07/18/2022] [Indexed: 11/22/2023] Open
Abstract
Autophagy is a conserved cellular self-digesting process that degrades obsoleting proteins and cellular components and plays a crucial role in the tumorigenesis, metastasis, and drug resistance of various tumors such as gastric cancer (GC). As a hotspot in molecular biology, non-coding RNAs (ncRNAs) are involved in the regulation of multiple biological processes, such as autophagy. Increasing evidence indicate that various ncRNAs exert double roles in the initiation and progression of GC, either serve as oncogenes or tumor suppressors. Recent studies have shown that some ncRNAs could modulate autophagy activity in GC cells, which would affect the malignant transformation and drug resistance. Whether the function of ncRNAs in GC is dependent on autophagy is undefined. Therefore, identifying the underlying moleculr targets of ncRNAs in autophagy pathways and the role of ncRNA-regulated autophagy in GC could develop new treatment interventions for this disease. This review summarizes the autophagy process and its role in GC, and the regulatory mechanisms of ncRNAs, as well as focuses on the dual role of ncRNAs-mediated autophagy in GC, for the development of potential therapeutic strategies in GC patients.
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Affiliation(s)
- Zijian Wang
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jiarui Liu
- College of Life Science and Technology, Guangxi University, Nanning, China
| | - Jingri Xie
- Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xingxing Yuan
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Bingyu Wang
- Graduate College, Heilongjiang University of Chinese Medicine, Harbin, China
- Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China
| | - Wenjuan Shen
- Department of Gynaecology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yang Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China
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6
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Lu L, Liang Q, Zhang X, Xu Y, Meng D, Liang Z. Autophagy Related Noncoding RNAs: Emerging Regulatory Factors of Gastric Cancer. Cancer Manag Res 2022; 14:2215-2224. [PMID: 35898946 PMCID: PMC9309173 DOI: 10.2147/cmar.s364761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 07/12/2022] [Indexed: 11/29/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant cancers that seriously affect human health. Autophagy is a highly conserved self-defense mechanism found to plays an important role in the occurrence, progression, drug resistance, and prognosis of GC. Noncoding RNAs (ncRNAs) play a critical role in the occurrence and development of a variety of diseases including GC. In recent years, increasing attention has been given to research on autophagy-related ncRNAs, such as miRNA, lncRNA, and circRNA in GC. Herein, we briefly summarize the roles, functions, and the research progress of autophagy and autophagy-related ncRNAs in GC with a focus on the potential application in GC tumorigenesis, development, prognosis, and drug resistance. We also discussed prospects of clinical application, future research direction, and challenges in future research of autophagy-related ncRNAs.
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Affiliation(s)
- Ling Lu
- Child Healthcare Department, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
| | - Qiaoyan Liang
- Health Care Department, People’s Liberation Army Navy No. 971 Hospital, Qingdao, People’s Republic of China
| | - Xinyi Zhang
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
| | - Yumeng Xu
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
| | - Dehua Meng
- Department of Allergy, Dongtai People’s Hospital, Yancheng, People’s Republic of China
| | - Zhaofeng Liang
- School of Medicine, Jiangsu University, Zhenjiang, People’s Republic of China
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7
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Tang SY, Zhou PJ, Meng Y, Zeng FR, Deng GT. Gastric cancer: An epigenetic view. World J Gastrointest Oncol 2022; 14:90-109. [PMID: 35116105 PMCID: PMC8790429 DOI: 10.4251/wjgo.v14.i1.90] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/17/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) poses a serious threat worldwide with unfavorable prognosis mainly due to late diagnosis and limited therapies. Therefore, precise molecular classification and search for potential targets are required for diagnosis and treatment, as GC is complicated and heterogeneous in nature. Accumulating evidence indicates that epigenetics plays a vital role in gastric carcinogenesis and progression, including histone modifications, DNA methylation and non-coding RNAs. Epigenetic biomarkers and drugs are currently under intensive evaluations to ensure efficient clinical utility in GC. In this review, key epigenetic alterations and related functions and mechanisms are summarized in GC. We focus on integration of existing epigenetic findings in GC for the bench-to-bedside translation of some pivotal epigenetic alterations into clinical practice and also describe the vacant field waiting for investigation.
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Affiliation(s)
- Si-Yuan Tang
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Pei-Jun Zhou
- Cancer Research Institute, School of Basic Medicine Science, Central South University, School of Basic Medicine Science, Central South University 410008, Hunan Province, China
| | - Yu Meng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Fu-Rong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
| | - Guang-Tong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
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8
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Koustas E, Trifylli EM, Sarantis P, Kontolatis NI, Damaskos C, Garmpis N, Vallilas C, Garmpi A, Papavassiliou AG, Karamouzis MV. The Implication of Autophagy in Gastric Cancer Progression. Life (Basel) 2021; 11:1304. [PMID: 34947835 PMCID: PMC8705750 DOI: 10.3390/life11121304] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/23/2021] [Accepted: 11/25/2021] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients.
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Affiliation(s)
- Evangelos Koustas
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Eleni-Myrto Trifylli
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Panagiotis Sarantis
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Nikolaos I. Kontolatis
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Christos Damaskos
- Renal Transplantation Unit, ‘Laiko’ General Hospital, 11527 Athens, Greece;
- ‘N.S. Christeas’ Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Nikolaos Garmpis
- ‘N.S. Christeas’ Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
- Second Department of Propedeutic Surgery, ‘Laiko’ General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Christos Vallilas
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Anna Garmpi
- First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece;
| | - Athanasios G. Papavassiliou
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
| | - Michalis V. Karamouzis
- Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (E.-M.T.); (P.S.); (N.I.K.); (C.V.); (A.G.P.); (M.V.K.)
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9
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Chen Q, Li Z, Xu Z, Chen C, Wang J, Zhu J, Dong Z. miR-378d is Involved in the Regulation of Apoptosis and Autophagy of and E 2 Secretion from Cultured Ovarian Granular Cells Treated by Sodium Fluoride. Biol Trace Elem Res 2021; 199:4119-4128. [PMID: 33405077 DOI: 10.1007/s12011-020-02524-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Accepted: 11/29/2020] [Indexed: 11/28/2022]
Abstract
Taking excessive sodium fluoride may cause female reproductive dysfunction, but underlying molecular mechanism is unclear. The ovarian granulosa cells are the key endocrine cells releasing reproductive hormones. The miRNAs in the granulosa cells play an important function in regulating reproduction. The aim of this study is to explore the role of miRNAs in granulosa cell apoptosis and autophagy, as well as estradiol (E2) release in response to excessive sodium fluoride. The ovarian granulosa cells (KGN cells) were treated in vitro by different concentrations of sodium fluoride (NaF) for 24 h. The level of estradiol (E2) in the incubation medium was measured by ELISA kits. The total RNA and protein were collected and purified from KGN cells. The expression of miRNAs was detected by the real-time PCR. The signal molecules involved in cell apoptosis and autophagy were detected by the real-time PCR and Western blotting. Six miRNAs in granulosa cells were significantly up- or downregulated by NaF and selected for real-time PCR analysis. The miR-378d was the most significantly upregulated one dose dependently by NaF. It was positively correlated to the extent of apoptosis but negatively correlated to the level of autophagy in KGN cells in response to NaF. In addition, miR-378d promoted E2 release in response to 1 and 2 mM NaF but reduced E2 release in response to 4 and 8 mM NaF treatments. It is concluded that expression of miR-378d in ovarian granulosa cells is negatively correlated to the autophagy and E2 release and positively correlated to cell apoptosis under the influence of NaF.
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Affiliation(s)
- Qun Chen
- Institute of Endemic Diseases, Key Laboratory of Trace Elements and Endemic Diseases, National Health Commission of the People's Republic of China, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.
| | - Zhen Li
- Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhao Xu
- School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Chen Chen
- Endocrinology, School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Jiawei Wang
- Guipei class 84, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Jinyuan Zhu
- Kouqiang class 73, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China
| | - Zhaoheng Dong
- Shandong Shenghua Electronic New Materials Co., Ltd., Yantai, Shandong, China
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10
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Das S, Shukla N, Singh SS, Kushwaha S, Shrivastava R. Mechanism of interaction between autophagy and apoptosis in cancer. Apoptosis 2021; 26:512-533. [PMID: 34510317 DOI: 10.1007/s10495-021-01687-9] [Citation(s) in RCA: 134] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2021] [Indexed: 12/13/2022]
Abstract
The mechanisms of two programmed cell death pathways, autophagy, and apoptosis, are extensively focused areas of research in the context of cancer. Both the catabolic pathways play a significant role in maintaining cellular as well as organismal homeostasis. Autophagy facilitates this by degradation and elimination of misfolded proteins and damaged organelles, while apoptosis induces canonical cell death in response to various stimuli. Ideally, both autophagy and apoptosis have a role in tumor suppression, as autophagy helps in eliminating the tumor cells, and apoptosis prevents their survival. However, as cancer proceeds, autophagy exhibits a dual role by enhancing cancer cell survival in response to stress conditions like hypoxia, thereby promoting chemoresistance to the tumor cells. Thus, any inadequacy in either of their levels can lead to tumor progression. A complex array of biomarkers is involved in maintaining coordination between the two by acting as either positive or negative regulators of one or both of these pathways of cell death. The resulting crosstalk between the two and its role in influencing the survival or death of malignant cells makes it quintessential, among other challenges facing chemotherapeutic treatment of cancer. In view of this, the present review aims to highlight some of the factors involved in maintaining their diaphony and stresses the importance of inhibition of cytoprotective autophagy and deletion of the intermediate pathways involved to facilitate tumor cell death. This will pave the way for future prospects in designing drug combinations facilitating the synergistic effect of autophagy and apoptosis in achieving cancer cell death.
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Affiliation(s)
- Shreya Das
- Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani Campus, Pilani, Rajasthan, 333031, India
| | - Nidhi Shukla
- Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
| | | | - Sapana Kushwaha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, 226025, India
| | - Richa Shrivastava
- Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani Campus, Pilani, Rajasthan, 333031, India.
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11
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Xiu T, Guo Q, Jing FB. Facing Cell Autophagy in Gastric Cancer - What Do We Know so Far? Int J Gen Med 2021; 14:1647-1659. [PMID: 33976565 PMCID: PMC8104978 DOI: 10.2147/ijgm.s298705] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 03/12/2021] [Indexed: 01/17/2023] Open
Abstract
Autophagy is a process by which misfolded proteins and damaged organelles in the lysosomes of tumor cells were degraded reusing decomposed substances and avoiding accumulation of large amounts of harmful substances. Here, the role of autophagy in the development of malignant transformation of gastric tumors, and the underlying mechanisms involved in autophagy formation, and the application of targeted autophagy in the treatment of gastric cancer were summarized.
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Affiliation(s)
- Ting Xiu
- Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People's Republic of China.,Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, 266021, People's Republic of China
| | - Qie Guo
- Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People's Republic of China
| | - Fan-Bo Jing
- Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266003, People's Republic of China
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12
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Shan C, Chen X, Cai H, Hao X, Li J, Zhang Y, Gao J, Zhou Z, Li X, Liu C, Li P, Wang K. The Emerging Roles of Autophagy-Related MicroRNAs in Cancer. Int J Biol Sci 2021; 17:134-150. [PMID: 33390839 PMCID: PMC7757044 DOI: 10.7150/ijbs.50773] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 10/29/2020] [Indexed: 12/11/2022] Open
Abstract
Autophagy is a conserved catabolic process involving the degradation and recycling of damaged biomacromolecules or organelles through lysosomal-dependent pathways and plays a crucial role in maintaining cell homeostasis. Consequently, abnormal autophagy is associated with multiple diseases, such as infectious diseases, neurodegenerative diseases and cancer. Currently, autophagy is considered to be a dual regulator in cancer, functioning as a suppressor in the early stage while supporting the growth and metastasis of cancer cells in the later stage and may also produce therapeutic resistance. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level by silencing targeted mRNA. MiRNAs have great regulatory potential for several fundamental biological processes, including autophagy. In recent years, an increasing number of studies have linked miRNA dysfunction to the growth, metabolism, migration, metastasis, and responses of cancer cells to therapy. Therefore, the study of autophagy-related miRNAs in cancer will provide insights into cancer biology and lead to the development of novel anti-cancer strategies. In the present review, we summarise the current knowledge of miRNA dysregulation during autophagy in cancer, focusing on the relationship between autophagy and miRNAs, and discuss their involvement in cancer biology and cancer treatment.
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Affiliation(s)
- Chan Shan
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xinzhe Chen
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Hongjing Cai
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xiaodan Hao
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Jing Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Yinfeng Zhang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Jinning Gao
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Zhixia Zhou
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Xinmin Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Cuiyun Liu
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Peifeng Li
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
| | - Kun Wang
- Institute of Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao 266021, China
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Cao D, Di M, Liang J, Shi S, Tan Q, Wang Z. MicroRNA-183 in Cancer Progression. J Cancer 2020; 11:1315-1324. [PMID: 32047538 PMCID: PMC6995398 DOI: 10.7150/jca.39044] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/16/2019] [Indexed: 12/15/2022] Open
Abstract
MicroRNA-183(miR-183) is abnormally expressed in many kinds of tumors. It participates in the initiation and development of tumors. There are many pathways regulate the expression of miR-183. The action mechanism of miR-183 in cancer is very extensive, and contradictory conclusions are often drawn. It was upregulated in 18 kinds of cancer, downregulated in 6 kinds of cancer. In addition, there are seven types of cancer, both upregulated and downregulated reports can be found. Evidence showed that miR-183 can not only directly play the role of oncogene or antioncogene, but also regulate the expression of other oncogene or antioncogene in different cancer types. In this review, we discuss the regulator of miR-183 and summarized the expression of miR-183 in different cancers. We also counted the target genes of miR-183 and the functional roles they play. Furthermore, we focused on the roles of miR-183 in cell migration, cell invasion, epithelial-mesenchymal transition (EMT) and microangiogenesis, which play the most important roles in cancer processes. It sheds light on the likely reasons why miR-183 plays different roles in various cancers. In addition, miR-183 and its downstream effectors have the potential to be promising prognostic markers and therapeutic targets in cancer.
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Affiliation(s)
- Dingren Cao
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Min Di
- Sir Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, 310058, P. R. China
| | - Jingjie Liang
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Shuang Shi
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Qiang Tan
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
| | - Zhengguang Wang
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, P. R. China
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14
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Huang R, Xiang J, Zhou P. Vitamin D, gut microbiota, and radiation-related resistance: a love-hate triangle. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2019; 38:493. [PMID: 31843023 PMCID: PMC6915920 DOI: 10.1186/s13046-019-1499-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Accepted: 12/04/2019] [Indexed: 12/12/2022]
Abstract
Radiation resistance is a serious issue in radiotherapy. Increasing evidence indicates that the human gut microbiome plays a role in the development of radiation resistance. Vitamin D is an important supplement for cancer patients treated with radiotherapy. Against this background, this paper reviewed research regarding the associations among vitamin D, microbiota dysbiosis, and radiation resistance. A hypothesis is developed to describe the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes. Radiotherapy changes the composition of the gut microbiota, which in turn influence the serum level of vitamin D, and its distribution and metabolism in the body. Alteration of vitamin D level influences the patient response to radiotherapy, where the underlying mechanisms may be associated with the intestinal microenvironment, immune molecules in the intestines, gut microbiome metabolites, and signaling pathways associated with vitamin D receptors. Our understanding of the contribution of vitamin D and the gut microbiota to radiotherapy outcomes has been increasing gradually. A better understanding of the relationships among vitamin D, the gut microbiota, and radiotherapy outcomes will shed more light on radiation resistance, and also promote the development of new strategies for overcoming it, thus addressing an important challenge associated with the currently available radiotherapy modalities for cancer patients.
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Affiliation(s)
- Ruixue Huang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, Hunan Province, China
| | - Jing Xiang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, 410078, Hunan Province, China
| | - Pingkun Zhou
- Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory, School of Public Health, Guangzhou Medical University, Guangzhou, 511436, People's Republic of China. .,Department of Radiation Biology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, AMMS, Beijing, 100850, China.
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