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      Knockdown of circ-PVT1 inhibits the progression of lung adenocarcinoma and enhances the sensitivity to cisplatin via the miR-429/FOXK1 signaling axis

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          Abstract

          Lung cancer is one of the most prevalent cancers in China, and its incidence and morbidity remain high due to various independent factors. Lung adenocarcinoma (ADC) is the most common type of non-small cell lung carcinoma. Circular RNA plasmacytoma variant translocation 1 (circ-PVT1) plays an oncogenic role in various types of cancer, but the specific role of circ-PVT1 in lung ADC has not yet been reported. In the present study, circ-PVT1 was knocked down in A549 cells and the cell viability, proliferation, migration and invasion were measured via MTT, colony formation, wound healing and Transwell assays, respectively. Then, the cell viability of A549 cells with circ-PVT1-knockdown or -overexpression was detected after exposure to cisplatin (DDP). After confirming the associations among circ-PVT1, microRNA (miR)-429 and forkhead box k1 (FOXK1) using various tools and assays, the cellular functions of A549 cells treated with combined short hairpin (sh)RNA-circ-PVT1 and miR-429 inhibitor/pcDNA3.1-FOXK1 were tested again. The expression of circ-PVT1 was found to be increased in lung ADC cells, and shRNA-circ-PVT1 led to decreased cell viability, proliferation, migration and invasion. The expression of circ-PVT1 was higher in A549/DDP cells than that in A549 cells, and the activity of caspase-3 was also activated by DDP in A549/DDP cells transfected with shRNA-circ-PVT1, whereas it was inactivated by DDP in A549 cells transfected with circ-PVT1 overexpression plasmid. Furthermore, the decreased cell viability, proliferation, invasion and migration induced by shRNA-circ-PVT1 could be abated by transfection with miR-429 inhibitor and pcDNA3.1-FOXK1. In conclusion, interference of circ-PVT1 inhibits the progression of lung ADC and enhances its sensitivity to DDP via miR-429/FOXK1, which may provide a theoretical basis for the use of novel targets in the treatment of lung ADC.

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          Kenneth Livak, Thomas D. Schmittgen (2001)
          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            Cancer statistics, 2018

            Kimberly D Miller, Rebecca Siegel, Ahmedin Jemal (2018)
            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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              Circular RNA: A new star of noncoding RNAs.

              Shibin Qu, Xisheng Yang, Xiaolei Li … (2015)
              Circular RNAs (circRNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent studies have discovered thousands of endogenous circRNAs in mammalian cells. CircRNAs are largely generated from exonic or intronic sequences, and reverse complementary sequences or RNA-binding proteins (RBPs) are necessary for circRNA biogenesis. The majority of circRNAs are conserved across species, are stable and resistant to RNase R, and often exhibit tissue/developmental-stage-specific expression. Recent research has revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, and modifiers of parental gene expression. Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases. Similar to miRNAs and long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the field of RNA and could be widely involved in the processes of life. Herein, we review the formation and properties of circRNAs, their functions, and their potential significance in disease.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mol Med Rep
                Journal ID (iso-abbrev): Mol Med Rep
                Title: Molecular Medicine Reports
                Publisher: D.A. Spandidos
                ISSN (Print): 1791-2997
                ISSN (Electronic): 1791-3004
                Publication date (Print): October 2021
                Publication date (Electronic): 29 July 2021
                Publication date PMC-release: 29 July 2021
                Volume: 24
                Issue: 4
                Electronic Location Identifier: 684
                Affiliations
                [1 ]Department of Respiratory Medicine, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu 222023, P.R. China
                [2 ]Department of Oncology, The Affiliated Hospital of Nantong University, Dongtai, Jiangsu 224200, P.R. China
                [3 ]Department of Pharmacy, The Affiliated Hospital of Nantong University, Dongtai, Jiangsu 224200, P.R. China
                Author notes
                Correspondence to: Dr Dongyun Gao, Department of Oncology, The Affiliated Hospital of Nantong University, 2 Kangfu West Road, Dongtai, Jiangsu 224200, P.R. China, E-mail: gaodongyungdy@ 123456163.com
                Article
                Publisher ID: MMR-0-0-12323
                DOI: 10.3892/mmr.2021.12323
                PMC ID: 8365593
                PubMed ID: 34328193
                SO-VID: e4c79ea7-1122-4ddf-89f2-8baec836b0df
                Copyright © Copyright: © Cao et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                Date received : 25 January 2021
                Date accepted : 20 April 2021
                Funding
                Funded by: General Program of National Natural Science Foundation of China
                Award ID: 81671905
                The present study was funded by the General Program of National Natural Science Foundation of China (grant no. 81671905).
                Categories
                Subject: Articles

                Keywords: circrna plasmacytoma variant translocation 1,lung adenocarcinoma,cisplatin,microrna-429,forkhead box k1
                Data availability:
                Keywords: circrna plasmacytoma variant translocation 1, lung adenocarcinoma, cisplatin, microrna-429, forkhead box k1

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