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Chuang YT, Yen CY, Tang JY, Chang FR, Tsai YH, Wu KC, Chien TM, Chang HW. Protein phosphatase 2A modulation and connection with miRNAs and natural products. ENVIRONMENTAL TOXICOLOGY 2024; 39:3612-3627. [PMID: 38491812 DOI: 10.1002/tox.24199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/28/2024] [Accepted: 02/10/2024] [Indexed: 03/18/2024]
Abstract
Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.
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Affiliation(s)
- Ya-Ting Chuang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yu Yen
- School of Dentistry, Taipei Medical University, Taipei, Taiwan
- Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jen-Yang Tang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hong Tsai
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan
| | - Kuo-Chuan Wu
- Department of Computer Science and Information Engineering, National Pingtung University, Pingtung, Taiwan
| | - Tsu-Ming Chien
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Raji GR, Poyyakkara A, Sruthi TV, Edatt L, Haritha K, Shankar SS, Kumar VBS. Horizontal transfer of miR-383 sensitise cells to cisplatin by targeting VEGFA-Akt signalling loop. Mol Biol Rep 2024; 51:286. [PMID: 38329638 DOI: 10.1007/s11033-023-09195-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/20/2023] [Indexed: 02/09/2024]
Abstract
BACKGROUND Cellular resistance to cisplatin has been one of the major obstacles in the success of combination therapy for many types of cancers. Emerging evidences suggest that exosomes released by drug resistant tumour cells play significant role in conferring resistance to drug sensitive cells by means of horizontal transfer of genetic materials such as miRNAs. Though exosomal miRNAs have been reported to confer drug resistance, the exact underlying mechanisms are still unclear. METHODS AND RESULTS In the present study, mature miRNAs secreted differentially by cisplatin resistant and cisplatin sensitive HepG2 cells were profiled and the effect of most significantly lowered miRNA in conferring cisplatin resistance when horizontally transferred, was analysed. we report miR-383 to be present at the lowest levels among the differentially abundant miRNAs expressed in exosomes secreted by cisplatin resistant cells compared to that that of cisplatin sensitive cells. We therefore, checked the effect of ectopic expression of miR-383 in altering cisplatin sensitivity of Hela cells. Drug sensitivity assay and apoptotic assays revealed that miR-383 could sensitise cells to cisplatin by targeting VEGF and its downstream Akt mediated pathway. CONCLUSION Results presented here provide evidence for the important role of miR-383 in regulating cisplatin sensitivity by modulating VEGF signalling loop upon horizontal transfer across different cell types.
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Affiliation(s)
- Grace R Raji
- Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Kasaragod, Kerala, 671316, India
| | - Aswini Poyyakkara
- Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Kasaragod, Kerala, 671316, India
| | - T V Sruthi
- Department of Medicine, Thomas Jefferson University, Jefferson Alumni Hall, 1020 Locust Street, Philadelphia, PA, 19107, USA
| | - Lincy Edatt
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27516, USA
| | - K Haritha
- Department of Pediatrics, Neurooncology Division and Aflac Cancer and Blood Disorders Centre of Childrens Healthcare of Atlanta, Emory University, Atlanta, GA, 30322, USA
| | - S Sharath Shankar
- Department of Medicine, Thomas Jefferson University, Jefferson Alumni Hall, 1020 Locust Street, Philadelphia, PA, 19107, USA
| | - V B Sameer Kumar
- Department of Genomic Science, School of Biological Sciences, Central University of Kerala, Kasaragod, Kerala, 671316, India.
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Zhao YX, Ma LB, Yang Z, Wang F, Wang HY, Dang JY. Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin. World J Gastrointest Oncol 2023; 15:286-302. [PMID: 36908323 PMCID: PMC9994047 DOI: 10.4251/wjgo.v15.i2.286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 11/23/2022] [Accepted: 01/05/2023] [Indexed: 02/14/2023] Open
Abstract
BACKGROUND Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly discovered oncogene. It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer (GC) cells. CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies. The underlying mechanism, however, is unknown. Further, the primary treatment regimen for GC is oxaliplatin-based chemotherapy. Nonetheless, it often fails due to chemoresistance of GC cells to oxaliplatin.
AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.
METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues. CIP2A expression in GC cell lines was reduced using small interfering RNA. After confirming the silencing efficiency, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment. Further, the key genes and protein changes were verified using real-time quantitative reverse transcription PCR and Western blotting, respectively, before and after intervention. For bioinformatics analysis, we used the R software and Bioconductor project. For statistical analysis, we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0 (IBM, Armonk, United States).
RESULTS A high level of CIP2A expression was associated with tumor size, T stage, lymph node metastasis, Tumor Node Metastasis stage, and a poor prognosis. Further, CIP2A expression was higher in GC cells than in normal human gastric epithelial cells. Using small interfering RNA against CIP2A, we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin. Moreover, CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells. Hence, high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin. In human GC cells, CIP2A regulated protein kinase B phosphorylation, and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin. Therefore, the protein kinase B signaling pathway was correlated with CIP2A-enhanced chemoresistance of human GC cells to oxaliplatin.
CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.
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Affiliation(s)
- Yong-Xun Zhao
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Li-Bin Ma
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Ze Yang
- The Seventh Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Fang Wang
- Department of Pathology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Hui-Ying Wang
- The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Jia-Yao Dang
- The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China
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Sun Z, Liu X, Lu M, Zhang X, Sun J. Serum-derived exosomes induce proinflammatory cytokines production in Cynoglossus semilaevis via miR-133-3p. DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY 2022; 136:104497. [PMID: 35921922 DOI: 10.1016/j.dci.2022.104497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/18/2022] [Accepted: 07/18/2022] [Indexed: 06/15/2023]
Abstract
Exosomes are small membrane-enclosed vesicles secreted by various types of cells. In mammals, a wide range of physiological and pathological functions have been confirmed and attributed to EVs carrying a variety of molecular cargoes, including miRNAs. However, studies on the biological functions and related molecular mechanisms of serum exosomes isolated from teleost fish are limited. Indeed, the molecular mechanisms underlying the effects of serum exosomes on immune responses and inflammatory processes are unknown. Chinese tongue sole (Cynoglossus semilaevis) is an economically important species used widely in industrial aquaculture. Vibrio harveyi, a common bacterial pathogen that infects C. semilaevis and some other fish, causes excessive inflammatory reactions, which are characterized by skin ulceration. Here, we isolated serum-derived exosomes from C. semilaevis and investigated their effects on inflammatory processes following V. harveyi infection. We found that compared with uninfected fish, exosome abundance in infected fish blood increased with bacterial infection time, while expression of TNF-α increased, and that of IL-10 decreased, significantly. Moreover, artificial infection studies demonstrated that injection of serum exosomes isolated from infected fish increased expression of TNF-α, IL-6, and IL-8, which is consistent with the increase in proinflammatory cytokines induced by V. harveyi infection. To further investigate the mechanisms by which exosomes increase proinflammatory cytokine production, we performed miRNA expression profiling and found that 26 differentially expressed miRNAs were associated with bacterial infection and immune responses; of these, miR-133-3p was considerably more abundant in serum exosomes from infected fish. Bioinformatics analysis suggested that miR-133-3p inhibits NF-κB signaling pathways by targeting PP2A and affecting cytokine release. We also found that miR-133-3p increased expression of TNF-α, IL-6, and IL-8 in fish blood and kidney, whereas an miR-133-3p inhibitor showed the opposite results. Thus, the data suggest that serum exosomes participate in innate immunity in teleost fish by promoting inflammatory responses to bacterial infection. Exosome-mediated transfer of miR-133-3p increases expression of proinflammatory cytokines in C. semilaevis, resulting in excessive inflammatory responses during V. harveyi infection. These data may lead to development of methods and strategies that control skin ulceration in Chinese tongue sole.
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Affiliation(s)
- Zhanpeng Sun
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China; Faculty of Education, Tianjin Normal University, Tianjin, China.
| | - Xiaozhu Liu
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
| | - Meiyi Lu
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
| | - Xiao Zhang
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
| | - Jinsheng Sun
- Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, China.
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Rout M, Kour B, Vuree S, Lulu SS, Medicherla KM, Suravajhala P. Diabetes mellitus susceptibility with varied diseased phenotypes and its comparison with phenome interactome networks. World J Clin Cases 2022; 10:5957-5964. [PMID: 35949812 PMCID: PMC9254192 DOI: 10.12998/wjcc.v10.i18.5957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 02/02/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
An emerging area of interest in understanding disease phenotypes is systems genomics. Complex diseases such as diabetes have played an important role towards understanding the susceptible genes and mutations. A wide number of methods have been employed and strategies such as polygenic risk score and allele frequencies have been useful, but understanding the candidate genes harboring those mutations is an unmet goal. In this perspective, using systems genomic approaches, we highlight the application of phenome-interactome networks in diabetes and provide deep insights. LINC01128, which we previously described as candidate for diabetes, is shown as an example to discuss the approach.
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Affiliation(s)
- Madhusmita Rout
- Department of Pediatrics, University of Oklahoma Health Sciences Centre, Oklahoma City, OK 73104, United States
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur 302001, Rajasthan, India
| | - Bhumandeep Kour
- Department of Biotechnology, Lovely Professional University, Phagwara 144001, Punjab, India
| | - Sugunakar Vuree
- Department of Biotechnology, Lovely Professional University, Phagwara 144001, Punjab, India
| | - Sajitha S Lulu
- Department of Biotechnology, Vellore Institute of Technology, Vellore 632014, Tamil Nadu, India
| | - Krishna Mohan Medicherla
- Department of Biotechnology and Bioinformatics, Birla Institute of Scientific Research, Jaipur 302001, Rajasthan, India
| | - Prashanth Suravajhala
- Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Vallikavu PO, Amritapuri, Clappana, Kollam 690525, Kerala, India
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Yi Q, Xie W, Sun W, Sun W, Liao Y. A Concise Review of MicroRNA-383: Exploring the Insights of Its Function in Tumorigenesis. J Cancer 2022; 13:313-324. [PMID: 34976192 PMCID: PMC8692686 DOI: 10.7150/jca.64846] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 11/10/2021] [Indexed: 12/15/2022] Open
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that commonly have 18-22 nucleotides and play important roles in the regulation of gene expression via directly binding to the 3'-UTR of target mRNAs. Approximately 50% of human genes are regulated by miRNAs and they are involved in many human diseases, including various types of cancers. Recently, microRNA-383 (miR-383) has been identified as being aberrantly expressed in multiple cancers, such as malignant melanoma, colorectal cancer, hepatocellular cancer, and glioma. Increasing evidence suggests that miR-383 participates in tumorigenic events including proliferation, apoptosis, invasion, and metastasis as well as drug resistance. Although downstream targets including CCND1, LDHA, VEGF, and IGF are illustrated to be regulated by miR-383, its roles in carcinogenesis are still ambiguous and the underlying mechanisms are still unclear. Herein, we review the latest studies on miR-383 and summarize its functions in human cancers and other diseases. The goal of this review is to provide new strategies for targeted therapy and further investigations.
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Affiliation(s)
- Qian Yi
- The Central Laboratory, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China.,Department of Physiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan province 646099, P.R. China.,Laboratory of Anesthesia and Organ Protection, Southwest Medical University, Luzhou, Sichuan province 646099, P.R. China
| | - Wei Xie
- Department of Orthopedics, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China
| | - Wei Sun
- Department of Orthopedics, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China
| | - Weichao Sun
- The Central Laboratory, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China.,Department of Orthopedics, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China
| | - Yi Liao
- The Central Laboratory, Shenzhen Second People's Hospital/First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518035, P.R. China
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Jafarzadeh A, Noori M, Sarrafzadeh S, Tamehri Zadeh SS, Nemati M, Chatrabnous N, Jafarzadeh S, Hamblin MR, Jafari Najaf Abadi MH, Mirzaei H. MicroRNA-383: A tumor suppressor miRNA in human cancer. Front Cell Dev Biol 2022; 10:955486. [PMID: 36313570 PMCID: PMC9608775 DOI: 10.3389/fcell.2022.955486] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/23/2022] [Indexed: 02/05/2023] Open
Abstract
Downregulated expression of anti-tumor miR-383 has been found in many kinds of cancer. MiR-383 family members can directly target the 3'-untranslated region (3'-UTR) of the mRNA of some pro-tumor genes to attenuate several cancer-related processes, including cell proliferation, invasion, migration, angiogenesis, immunosuppression, epithelial-mesenchymal transition, glycolysis, chemoresistance, and the development of cancer stem cells, whilst promoting apoptosis. Functionally, miR-383 operates as a tumor inhibitor miRNA in many types of cancer, including breast cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, colorectal cancer, esophageal cancer, lung cancer, head and neck cancer, glioma, medulloblastoma, melanoma, prostate cancer, cervical cancer, oral squamous cell carcinoma, thyroid cancer, and B-cell lymphoma. Both pro-tumor and anti-tumor effects have been attributed to miR-383 in ovarian cancer. However, only the pro-tumor effects of miR-383 were reported in cholangiocarcinoma. The restoration of miR-383 expression could be considered a possible treatment for cancer. This review discusses the anti-tumor effects of miR-383 in human cancers, emphasizing their downstream target genes and potential treatment approaches.
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Affiliation(s)
- Abdollah Jafarzadeh
- Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
- *Correspondence: Abdollah Jafarzadeh, ; Mohammad Hassan Jafari Najaf Abadi, ; Hamed Mirzaei,
| | - Majid Noori
- Golestan Hospital Research Center, AJA University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Sarrafzadeh
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Maryam Nemati
- Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
- Department of Hematology and Laboratory Sciences, School of Para-Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Nazanin Chatrabnous
- Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sara Jafarzadeh
- Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Johannesburg, South Africa
| | - Mohammad Hassan Jafari Najaf Abadi
- Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- *Correspondence: Abdollah Jafarzadeh, ; Mohammad Hassan Jafari Najaf Abadi, ; Hamed Mirzaei,
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
- Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
- *Correspondence: Abdollah Jafarzadeh, ; Mohammad Hassan Jafari Najaf Abadi, ; Hamed Mirzaei,
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Tao S, Gu J, Wang Q, Zheng L. Translational control of Bcl-2 promotes apoptosis of gastric carcinoma cells. BMC Cancer 2021; 21:12. [PMID: 33402109 PMCID: PMC7786514 DOI: 10.1186/s12885-020-07711-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 12/03/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Anti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study. METHODS We investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients' clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins. RESULTS The levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3'-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database. CONCLUSION MiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.
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Affiliation(s)
- Shuangfen Tao
- Oncology Department, Xin Hua Hospital affiliated To Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China
| | - Jianchun Gu
- Oncology Department, Xin Hua Hospital affiliated To Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China
| | - Qing Wang
- Oncology Department, Xin Hua Hospital affiliated To Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China
| | - Leizhen Zheng
- Oncology Department, Xin Hua Hospital affiliated To Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
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Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals. Molecules 2020; 25:molecules25204701. [PMID: 33066509 PMCID: PMC7587345 DOI: 10.3390/molecules25204701] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023] Open
Abstract
Cancer is a global health concern and one of the main causes of disease-related death. Even with considerable progress in investigations on cancer therapy, effective anti-cancer agents and regimens have thus far been insufficient. There has been compelling evidence that natural phytochemicals and their derivatives have potent anti-cancer activities. Plant-based anti-cancer agents, such as etoposide, irinotecan, paclitaxel, and vincristine, are currently being applied in medical treatments for patients with cancer. Further, the efficacy of plenty of phytochemicals has been evaluated to discover a promising candidate for cancer therapy. For developing more effective cancer therapy, it is required to apprehend the molecular mechanism deployed by natural compounds. MicroRNAs (miRNAs) have been realized to play a pivotal role in regulating cellular signaling pathways, affecting the efficacy of therapeutic agents in cancer. This review presents a feature of phytochemicals with anti-cancer activity, focusing mainly on the relationship between phytochemicals and miRNAs, with insights into the role of miRNAs as the mediators and the regulators of anti-cancer effects of phytochemicals.
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