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Öğe Bibliometric Analysis of Multiple Sclerosis Studies in Pharmacology Journals(2024) Özkan, Mazhar; Yüksel, Tuğba Nurcan; Tozoğlu, FatihMultiple sclerosis (MS) is a prevalent neurological disease with a global impact on patients' lives. Our study aimed to conduct a bibliometric analysis of research published in the field of pharmacology over the past decade. We retrieved original articles on MS from pharmacology journals in the last ten years through the Scopus database. The collected data underwent analysis using VOSViewer software, examining relationships between studies based on parameters such as citation, authorship, and organizations. In our country-based analysis, the United States emerged with the highest document count, totaling 350, followed by Germany with 210 documents. Claudio Viegas holds the top position with four publications in the last decade. The most prolific organization identified was associated with the Biogen-Cambridge-MA-United States group. However, Chulalongkorn University in Bangkok, Thailand, specifically the Department of Psychiatry, received the most citations. The most cited document was \"Therapeutic Advances in Neurological Disorders,\" while the study with the highest citations was Ferreria-Vieira et al.'s (2016) work published in Current Neuropharmacology. Research efforts on MS treatment are evidently growing, with diverse research groups contributing worldwide. We anticipate that our study will provide valuable guidance to researchers in the field by shedding light on significant research and their interconnections in recent years.Öğe Early administration of milrinone ameliorates lung and kidney injury during sepsis in juvenile rats(Wiley, 2022) Keskin, Halil; Tavacı, Taha; Halıcı, Hamza; Yüksel, Tuğba Nurcan; Özkaraca, Mustafa; Bilen, Arzu; Halıcı, ZekaiBackground A sepsis model was created, induced by cecal ligation and puncture (CLP), in juvenile rat groups. Milrinone (MIL), which is known to have a modulatory effect on pro-inflammatory cytokines, was administered to the designated rat groups in the early period before severe sepsis developed. The study was aimed at investigating the possible protective effects of milrinone on the lung and kidney tissues of rats in the late phase of sepsis. Methods The rat pups were divided into seven groups with six animals in each group: (1) healthy rats who received no drug; (2) CLP-S12 (sacrificed at hour 12); (3) CLP-S24 (sacrificed at hour 24); (4) CLP-MIL1-S12 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 12); (5) CLP-MIL1-S24 (administered with 0.5 mg/kg milrinone at hour 1 and sacrificed at hour 24): (6) CLP-MIL12-S24 (administered with 0.5 mg/kg milrinone at hour 12 and sacrificed at hour 24), (7) and CLP-MIL1,12-S24 (administered with 0.5 mg/kg milrinone at hours 1 and 12 and sacrificed at hour 24). Results Significant differences were found between the early and late administration of milrinone in terms of both molecular and histopathological results. The results showed that the tissues were significantly preserved in the groups in which milrinone had been started in the early period compared to the sepsis control groups and the groups in which milrinone had been started in the late period. Conclusions In addition to the positive inotropic effects of milrinone, its immunomodulatory properties that result in decreased cytokine storm can be beneficial during early period of sepsis.Öğe Glutamat İle İndüklenen Nöron Hasarında Floretin ve Florizinin Etkileri: İn Vitro Çalışma(2019) Binnetoğlu, Damla; Yayla, Muhammed; Yüksel, Tuğba NurcanAmaç:Çalışmamızda eksitatör bir nörotransmitter olan glutamata bağlı nörotoksisitenin önlenmesi amacıyla güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin etkilerini araştırmayı amaçladık.Materyal ve Metot:Çalışmamızda yeni doğan sıçan korteksi kullanıldı. 10-5 M ve 2x10-5 M konsantrasyonlarında floretin ile 10-5 M ve 2x10-5 M konsantrasyonlarında florizin ayrı ayrı uygulandıktan 2 saat sonra 3x10-3 M ve 6x10-3 M konsantrasyonlarında glutamat uygulaması gerçekleştirildi. Glutamat uygulamasından 6 saat sonra hücrelerden mRNA izolasyonu yapıldı. 24 saat sonra ise metiltiazol difenil tetrazolium (MTT) testi, total oksidan ve antioksidan kapasite ölçümleri gerçekleştirildi.Bulgular:Çalışmamızda glutamat artan dozlarda hücre canlılığını azaltırken floretin ve florizin uygulaması yüksek dozda en iyi nöroprotektif etkiyi ortaya koydu. Toksisiteye bağlı artan total oksidan düzey floretin ve florizin tarafından anlamlı derecede düzeltildi. Toksisite oluşturulan grupta azalan antioksidan kapasite floretin ve florizin uygulaması ile düzelme gösterdi. Floretin ve florizin tek başlarına uygulandığında hücre canlılığını anlamlı derecede etkilemezken, antioksidan kapasiteyi artırdı, oksidan düzeyi ise azalttı. Glutamat uygulaması sonrası artan tümör nekroz faktör-alfa (TNF-?) mRNA ekspresyonu, floretin ve florizin uygulaması ile anlamlı derecede azaldı. Glutamat uygulamasına bağlı artan kaspaz 9 ve kaspaz 3 mRNA ekspresyonu ise floretin ve florizin uygulaması ile anlamlı derecede düzelmegösterdi.Sonuç:Bu bulgular, güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin glutamata bağlı gelişen nörotoksisitede koruyucu olabileceğini ve glutamatın neden olduğu nörolojik bozuklukların önlenmesi için terapötik ajanlar olarak kullanılabileceğini gösterir.Öğe INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS(2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köse, Duygu; Ugan, Rüstem Anıl; Tokay, Erdem; Kılıcle, Pınar Aksu; Çadırcı, ElifPomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 ?g/kg LPS, the dexamethasone (DEX) group received 200 ?g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 ?g/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-?, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.Öğe Neuroprotective effect of roflumilast under cerebral ischaemia/reperfusion injury in juvenile rats through NLRP-mediated inflammatory response inhibition(Wiley, 2021) Keskin, Halil; Keskin, Filiz; Tavaci, Taha; Halıcı, Hamza; Yüksel, Tuğba Nurcan; Özkaraca, Mustafa; Halıcı, ZekaiThis study aims to investigate the protective effect of roflumilast, a phosphodiesterase (PDE)-4 enzyme inhibitor, and demonstrate its possible role in the development prevention of cerebral ischemia/reperfusion injury (CI/RI) after stroke induced by carotid artery ligation in juvenile rats. The rats were randomly divided into five groups: healthy group without any treatment, healthy group administered with 1 mg/kg roflumilast, CI group not administered with roflumilast, CI group administered with 0.5 mg/kg roflumilast, and CI group administered with 1 mg/kg roflumilast. In the CI groups, reperfusion was achieved 2h after ischemia induction; in the roflumilast groups, this drug was intraperitoneally administered immediately after reperfusion and at the 12(th) hour. At the end of 24h, the rats were sacrificed and their brain tissues removed for examination. The mRNA expressions obtained with real-time PCR of IL-1 beta, TNF-alpha, and NLRP3 significantly increased in the CI/RI-induced groups compared with the control group, and this increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Moreover, ELISA revealed that both IL-1 beta and IL-6 brain levels were significantly higher in the CI/RI-induced groups than in the controls. This increase was significantly lower in the groups administered with roflumilast compared with the CI/RI-induced groups. Histopathological studies revealed that the values closest to those of the healthy group were obtained from the roflumilast groups. Nissl staining revealed that the Nissl bodies manifested normal density in the healthy and roflumilast-administered healthy groups, but were rare in the CI/RI-induced groups. Roflumilast treatment increased these decreased Nissl bodies with increasing doses. Observations indicated that the Nissl body density was close to the value in the healthy group in the CI/RI-induced group administered with 1 mg/kg roflumilast. Overall, roflumilast reduced cellular damage caused by CI/RI in juvenile rats, and this effect may be mediated by NLRP3.Öğe Protective effect of 5-HT7 receptor activation against glutamate-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via antioxidative and antiapoptotic pathways(Pergamon-Elsevier Science Ltd, 2019) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Halıcı, Zekai; Çadırcı, Elif; Polat, Beyzagül; Köse, DuyguSerotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-a) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 54-1T7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.Öğe Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage(Taylor & Francis Inc, 2022) Akpınar, Erol; Kutlu, Zerrin; Köse, Duygu; Aydın, Pelin; Tavacı, Taha; Bayraktutan, Zafer; Dinçer, Büşra; Yüksel, Tuğba NurcanBackground/Aims Sepsis is an uncontrolled systemic infection, withcomplex pathophysiology that may result in acute lung organ damage and cause multiple organ failure. Although much research has been conducted to illuminate sepsis's complex pathophysiology, sepsis treatment protocols are limited, and sepsis remains an important cause of mortality andmorbidity in intensive care units.Various studies have shown that idebenone (IDE) possesses strong antioxidant properties, which inhibit lipid peroxidation and protect cells from oxidative damage. The present study aimed to evaluate the protective effects of IDE against lung injury in a cecal ligation and puncture (CLP)-induced sepsis rat model. Methods Male albino Wistar rats were used. The animals were divided into a healthy control (no treatment), CLP, IDE control (200 mg/kg), and CLP + IDE subgroups (50 mg/kg, 100 mg/kg, and 200 mg/kg), with nine rats in each group.IDE was administered 1 h after CLP induction.To evaluate the protective effects of IDE, lung tissues were collected 16 h after sepsis for biochemical, immunohistochemical staining, and histopathological examination. Results IDE significantly ameliorated sepsis-induced disturbances in oxidative stress-related factors, with its effects increasing in accordance with the dose.IDE also abolished histopathological changes in lung tissues associated with CLP.Furthermore, interleukin 1 beta (IL-1 beta)and tumor necrosis factor-alpha (TNF-alpha) immunopositivity markedly decreased in the septic rats following IDE treatment. Conclusions IDE largely mitigated the inflammatory response in sepsis-induced lung injury by decreasing free radicals and preventing lipid peroxidation. The results suggest that IDE may represent a potential novel therapeutic drug for sepsis treatment.Öğe Protective effects of melatonin receptor agonists on endotoxin- induced uveitis in rats(Mashhad Univ Med Sciences, 2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köşe, Duygu; Halıcı, Zekai; Bozkurt, Erdinç; Toktay, ErdemObjective(s): Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 pg/kg lipopolysaccharide (LPS), SC), DEX group (200 pg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 pg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 pg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 pg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 pg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hour. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of Tumor Necrosis Factor-alpha (TNF-alpha), vascular endothelial growth factor(VEGF), and Caspase 3 and Caspase 9 mRNA expression), biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-alpha, VEGF, Caspase 9, and Caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.Öğe Protective Effects of Ramelteon on Acute Lung Injury in Endotoxin-Induced Sepsis in Rats(2023) Yüksel, Tuğba Nurcan; Köse, Duygu; Gürbüz, Muhammet Ali; Halıcı, Zekai; Canbolat, Fadime; Bozgeyik, EsraIntroduction: Sepsis is a life-threatening excessive systemic inflammatory reaction syndrome to infection that usually occurs in patients with bacteremia. The respiratory system is one of the structures most affected by acute organ damage. Melatonin plays an important role in re gulating various physiological functions of the body, including antioxidant and anti- inflammatory. Ramelteon (RAME) is the first melatonin receptor agonist confirmed for clinical use. The goal of this study is to determine the effects of RAME on endotoxin- induced septic lung injury in rats. Materials and Methods: Thirty-two female rats were separated randomly into four groups (n =8). Group healthy received intraperitoneal normal saline, group sepsis received intraperitoneally 10 mg/kg lipopolysaccharide (LPS), group sepsis+RAME2 received 10 mg/kg LPS plus 2mg/kg RAME, and group sepsis+RAME4 received 10 mg/kg LPS plus 4mg/kg RAME. RAME was administered by oral gavage 1 hour before LPS administration. The lung tissues were collected 12 hours after LPS administration and in vestigated molecularly (qRT- PCR analyses of Tumor Necrosis Factor-?, nuclear factor kappa-?, and interleukin 1-beta mRNA expression) and histopathologically (s taining with Harris Hematoxylin and Eosin Y). Results: TNF-?, NF- ??, and IL-1? levels significantly decreased dose-dependent in the septic rats following RAME administration. RAME admi nistration ameliorated histopathological injury in lung tissues due to sepsis. Conclusion: RAME ameliorated the inflammatory response in endotoxin-induced sepsis. These findings suggest that RAME can be a promising agent by contributing to alternative preventive treatment methods for sepsis with its anti- inflammatory effect.Öğe Sıçanlarda Renal İskemi/Reperfüzyon Hasarı Üzerine PDE 5 İnhibitörü-Avanafilin Etkisi(2023) Yüksel, Tuğba Nurcan; Halıcı, Zekai; Kaya, Cihangir; Bozkurt, Ayşe; Tavacı, Taha; Civelek, Maide Sena; Özdemir, BengülAmaç: Renal iskemi-reperfüzyon hasarı (RI/RI) başta böbrek olmak üzere birçok organa zarar verir. Fosfodiesteraz (PDE) 5 inhibitörleri, antioksidan ve anti-enflamatuvar etkilere sahiptir. Avanafil (AVA), daha yüksek PDE izoform seçiciliğine sahip ikinci nesil bir PDE 5 inhibitörüdür. Bu çalışmanın amacı sıçanlarda RI/RI üzerine AVA’nın etkilerini incelemektir. Gereç ve Yöntem: Kırk sıçan rastgele beş gruba (n=8) ayrıldı: Kontrol; AVA 10 mg/kg; RI/RI; RI/RI + 5 mg/kg AVA ve RI/RI + 10 mg/kg AVA. RI/RI sıçan modeli, renal arter klemplenerek oluşturuldu. Renal arter klempleme ile 45 dakika renal iskemi indüksiyonu ve ardından 24 saat reperfüzyon için akut bir cerrahi deney yapıldı. AVA, iskemiden 6 ve 1 saat önce oral olarak sonda ile uygulandı. Yirmi dört saatlik reperfüzyondan sonra moleküler ve biyokimyasal inceleme için böbrek dokuları çıkarıldı. Böbrek dokuları biyokimyasal [ELISA ile malondialdehit (MDA) ve glutatyon (GSH)], moleküler [qRT-PCR ile IL-1?, nükleer faktör-kappa B (NF-?B), and tümör nekroz faktörü-alfa (TNF-?) mRNA gen ekspresyonları] ve histopatolojik (Harris hematoksilen ve eosin Y ile boyama) olarak incelendi. Bulgular: AVA uygulaması, RI/RI’nin sebep olduğu MDA ve GSH düzeylerindeki değişiklikleri iyileştirdi. AVA tedavisi iskemi/reperfüzyon hasarından kaynaklanan böbrek dokularındaki IL-1?, NF-?B ve TNF-? mRNA gen ekspresyonlarındaki artışı düzeltti. AVA uygulaması renal iskemi reperfüzyonun neden olduğu böbrek dokularındaki histopatolojik hasarı iyileştirdi. Ayrıca kontrol grubuna en yakın değerler RI/RI’li sıçanlara 10 mg/kg AVA uygulanması ile elde edildi. Sonuç: AVA uygulaması, iskemi/reperfüzyon hasarında önemli olabilecek oksidatif stresi ve enflamatuvar kaskadları hafifleterek RI/RI kaynaklı doku hasarını iyileştirmiştir. Bu bulgular, RI/RI’yi tedavi etmek için AVA kullanımına ilişkin mekanik bir temel sağlayabilir.Öğe THE EFFECT OF QUERCETIN AND QUERCETIN-3-D-XYLOSIDE ON BREAST CANCER PROLIFERATION AND MIGRATION(Dokuz Eylul Univ Inst Health Sciences, 2022) Yüksel, Tuğba Nurcan; Bozgeyik, Esra; Yayla, MuhammedBackground and Purpose: The aim of this study is to investigate the migration, wound healing, colony formation, and cytotoxic effects of Quercetin-3-D-xyloside (reynoutrin), a quercetin derivative, in breast cancer cells Methods: In the present study, CRL-4010, MCF7 and MDA-MB-231 cells were used to evaluate the cytotoxic, antiproliferative and migration effects of reynoutrin on breast cancer. The IC50 concentration (400 mu g/ml) of reynoutrin, quercetin and cisplatin in the cells was determined. For cytotoxicity assessments, varying concentrations of quercetin, reynoutrin and cisplatin were applied and incubated 24h and 48h. In addition, to examine effects of reynoutrin on migration, cells were seeded in 6-well plates and incubated for 24 hours. For the colony formation assay cells were seeded to 12-well plates at a concentration of 1000 cells/well and incubated overnight. Results: These results indicated that reynoutrin markedly inhibit the cell viability in breast cancer. Conclusion: We have demonstrated for the first time with the present study that reynoutrin suppressed the progression of breast cancer cell proliferation induction and may provide a potential therapeutic target for breast cancer treatment. However, these results should be further confirmed by future more comprehensive studies.Öğe The Effects of Agomelatine Treatment on Lipopolysaccharide-Induced Septic Lung Injuries in Rats(Aves, 2021) Köse, Duygu; Yüksel, Tuğba Nurcan; Halıcı, Zekai; Çadırcı, Elif; Gürbüz, Muhammed AliObjective: We designed an experimental model of sepsis in rats to investigate the effects of agomelatine (AGO) on lung tissues using molecular and histopathological methods. Materials and Methods: In our experimental model, the 32 rats were divided into 4 groups: group 1: control group (HEALTHY); group 2: lipopolysaccharide group (LPS); group 3: LPS plus 50 mg/kg AGO group (LPS + AGO50); and group 4: LPS plus 100 mg/kg AGO group (LPS + AGO100). An LPS-induced sepsis model was performed to replicate the pathology of sepsis. Rats from all 4 groups were killed after 12 hours, and their lungs were quickly collected. To investigate the therapeutic strategy, we evaluated tumor necrosis factoralpha (TNF-alpha) and nuclear factor-kappa B (NF-kappa B) messenger RNA expressions by real-time polymerase chain reaction using molecular methods and lung tissue damage indicators using histopathological methods. Results: The expressions of TNF-alpha and NF-kappa B were reduced in the groups treated with AGO. The histopathology results supported the molecular results. Conclusion: In this experimental study, we demonstrated for the first time the positive effects of AGO on LPS-induced sepsis in lung tissue using molecular and histopathological methods, indicating that it contributes to the prevention of lung damage.Öğe The Role and Antagonistic Effects of miR-16-5p in the Regulation of ADP-Ribosylation Factor-Like Tumor Suppressor Gene 1 in Lung Cancer Cells(2023) Yüksel, Tuğba Nurcan; Bozgeyik, Esra; Bozgeyik, İbrahimObjective: ADP-ribosylation factor-like tumor suppressor gene 1 is a member of the Ras superfamily of small guanosine triphosphatases that are known to be involved in multiple regulatory pathways in the multistage development of human cancers. Also, ADP-ribosylation factor-like tumor suppressor gene 1 expression levels have been reported to be dramatically lower in both cancer cell lines and tumor tissues compared to con- trols. Accordingly, defects in the regulation of the ADP-ribosylation factor-like tumor suppressor gene 1 gene seems have key tumor suppressive effects in the formation and development of human cancers including lung cancer. Moreover, microRNAs regulating the expression of ADP-ribosylation factor-like tumor suppressor gene 1 have not been described previously. Accordingly, the present study aimed to reveal the influence of miR-16-5p on the regulation of ADP-ribosylation factor-like tumor suppressor gene 1 gene. Materials and Methods: A549 lung adenocarcinoma cells were used. For the overexpression and silencing experiments of miR-16-5p synthetic microRNA mimics and inhibitors were used, respectively. Gene expres- sion analyses were achieved with the help of quantitative real-time polymerase chain reaction. Results: MiR-16-5p was identified to be predictive target of ADP-ribosylation factor-like tumor suppressor gene 1 and directly targets the expression of ADP-ribosylation factor-like tumor suppressor gene 1 as revealed by the overexpression and silencing experiments. Specifically, it was found that miR-1 6-5p-overexpressed A549 cells showed a decrease in ADP-ribosylation factor-like tumor suppressor gene 1 gene expression, whereas miR- 16-5p-suppressed cells showed an increase in expression. These findings possibly suggest that miR-16-5p is the direct regulatory microRNA that posttranscriptionally regulates the expression of ADP-ribosylation factor-like tumor suppressor gene 1. Conclusion: Collectively, miR-16-5p seems to be a key regulatory molecule involved in the posttranscrip- tional regulation of the ADP-ribosylation factor-like tumor suppressor gene 1, and it might be responsible for the downregulation of this gene in lung cancer.
