lncRNA CASC15 Research Articles

Lncrna CASC15 Activated By TCF12 Promote Colorectal Cancer Progression via EMT.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors. Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC. Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT). We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression. Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.

LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424.

Study has demonstrated the abnormal expression and role of lncRNA CASC15 in diabetes patients with chronic renal failure. However, its role in diabetes nephropathy (DN) is still unclear. This study aimed to investigate the potential mechanism and role of lncRNA CASC15 in DN. The relationship between miR-424 and CASC15/SP-A was predicted by Starbase software and verified by luciferase reporter assay. HK-2 cells were treated with 25 mM glucose (HG) for 24 h to establish DN cell model. MTT and flow cytometry analysis were carried out to test cell proliferation and apoptosis. Epithelial-to-mesenchymal transition (EMT) markers were analyzed by RT-qPCR and western blot assay. We proved that CASC15 could interact with miR-424, and SP-A was a target of miR-424. HG-treatment significantly enhanced lncRNA CASC15 level and decreased miR-424 level in HK-2 cells. LncRNA CASC15-siRNA significantly improved cell viability, repressed apoptosis, promoted E-cadherin expression, and inhibited N-cadherin expression in HG-treated HK-2 cells, and these effects were reversed by miR-424 inhibitor. SP-A was highly expressed in HG-treated HK-2 cells. The biological effects of miR-424 mimic on HG-treated HK-2 cells were reversed by SP-A-plasmid. In conclusion, lncRNA CASC15 inhibition relieved HG-induced HK-2 cell injury and EMT through miR-424/SP-A axis.

Statement of Retraction: LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway

This article refers to:RETRACTED ARTICLE: LncRNA CASC11 promoted gastric cancer cell proliferation, migration and invasion in vitro by regulating cell cycle pathway

LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells.

Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low-density lipoprotein (ox-LDL)-induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox-LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real-time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit-8, flow cytometry, tube formation, and enzyme-linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox-LDL-induced injury of CMECs by binding to HuR and stabilizing HDAC4.

Correlation between plasma lncRNA CASC11 and malignancy in lung adenocarcinoma patients and the prognostic value of lncRNA CASC11.

Objective: To study the connection between lncRNA CASC11 plasma expression and clinical characteristics as well as prognoses of patients. Methods: Sixty lung adenocarcinoma (LUAD) patients and 60 healthy adults participated in this research. LncRNA CASC11 expression was detected by quantitativereal-time PCR and the relationships between lncRNA CASC11 plasma expression and patientprognosis and clinical characteristics wereanalyzed. Results: LncRNA CASC11 was highly expressed in LUAD tissues and plasma (p<0.05). Receiver operating characteristic curve analysis indicated the diagnostic value of lncRNA CASC11 in LUAD (p<0.0001). Higher plasma lncRNA CASC11 expression indicated worse patient prognoses (p<0.05). Plasma lncRNA CASC11 level was also closely related to tumor differentiation and tumor-node-metastasis stage (p<0.05). Conclusion: Plasma lncRNA CASC11 may be a potential biomarker for LUAD diagnosis and prognosis.

Lncrna CASC11 aggravates diabetic nephropathy via targeting FoxO1.

To explore the biological effects of CASC11 on aggravating diabetic nephropathy (DN) by regulating FoxO1 (forkhead transcription factor O1). Serum levels of CASC11 and FoxO1 in DN patients were detected. The possibility of CASC11 in predicting the onset of DN was analyzed by depicting ROC curves. Correlation between CASC11 and FoxO1 was evaluated by Pearson correlation test. After intervening CASC11 and FoxO1 levels, we found that changes in proliferative and migratory abilities in high glucose (HG)induced kidney mesangial cells were determined respectively. Protein levels of TGF-β1 and Smads regulated by both CASC11 and FoxO1 were examined by Western blot.

LncRNA-CASC15 knockdown inhibits the progression of esophageal squamous cell carcinoma through targeting miR-33a-5p/PTGS2 axis.

LncRNA CASC15 has been determined as a novel tumor-related lncRNA in many cancers. However, the in-detail role of CASC15 remains elusive in esophageal squamous cell carcinoma (ESCC). CASC15 expression level was detected in 113 ESCC tissues and paired adjacent normal tissues and in human ESCC cell lines. The effects of CASC15 on ESCC proliferation, migration, and invasion were assessed using CCK-8 and transwell assays. In addition, the potential downstream molecules of CASC15 were searched and confirmed by software algorithms, RT-qPCR, western blot, dual-luciferase reporter, and rescue experiments. CASC15 was upregulated in ESCC tissues and cell lines. CASC15 overexpression was associated with poorer prognosis in ESCC patients. Functionally, CASC15 knockdown inhibited cell proliferation, migration, and invasion of ESCC cells. Mechanistically, it was confirmed that CASC15 acts as competing endogenous RNA for miR-33a-5p to regulate PTGS2 expression. In addition, rescue assay showed that miR-33a-5p knockdown or PTGS2 overexpression abolished the cell proliferation, migration, and invasion inhibition role of CASC15 knockdown. In conclusion, this study indicates that CASC15 was upregulated in ESCC and CASC15 knockdown hindered ESCC progression through targeting the miR-33a-5p/PTGS2 axis. CASC15 might serve as a novel biomarker and therapeutic target for ESCC.

Clinical Significance of Low Expression of LncRNA CASC15 in Acute Myeloid Leukemia with NPM1 Mutations

Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis. The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival. The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.

LncRNA CASC15 regulates breast cancer cell stemness via the miR-654-5p/MEF2D axis.

Emerging evidence has demonstrated the prognostic and diagnostic potential of long noncoding RNA (lncRNA) cancer susceptibility candidate 15 (lncRNA CASC15) for the progression and tumorigenesis of human cancer. However, how CASC15 modulates the stemness of breast cancer stem cells (BCSCs) is not well understood. In this study, high expression of CASC15 in MCF-7 CSCs was reported, relative to MCF-7 cells, and this phenomenon was associated with metastatic lymph nodes, higher TNM stage, and shorter breast cancer survival rates. Further experiments revealed that CASC15 promoted the acquisition of stemness properties of breast cancer cells (BSCCs) by competing with endogenous RNA for miR-654-5p, resulting in overexpression of MEF2D in BCSCs. Overall, breast cancer stemness and tumor development are regulated via the CASC15/miR-654-5p/MEF2D axis. Accordingly, this pathway can be explored for breast cancer therapy.

A study of the prognostic value of long non-coding RNA CASC15 in human solid tumors utilizing The Cancer Genome Atlas (TCGA) datasets and a meta-analysis.

Several malignant solid tumors have been reported to have an abnormal expression of the long non-coding RNA CASC15 (lncRNA CASC15). However, the clinicopathologic and prognostic importance of CASC15 in solid tumors are unknown. As a result, we examined the interrelationship between CASC15, overall survival length, and clinicopathological attributes of cancers affecting humans by analyzing various studies and The Cancer Genome Atlas (TCGA) data related to CASC15 expression. Web of Science, PubMed, Cochrane Library, Embase, Chinese WanFang, and Chinese CNKI databases were used to conduct a literature search. Hazard ratios (HRs) and Pooled odds ratios (ORs) were calculated taking 95% confidence intervals (CIs). The results of the current meta-analysis were further validated using TCGA datasets. A total of 12 eligible studies enrolling 767 patients were included in this meta-analysis. Findings of the analysis showed that CASC15 expression had a significant relation to the metastasis of lymph node (OR = 3.30, 95%CI = 1.88-5.81, p < 0.001), distant metastasis (OR = 2.64, 95%CI = 1.24-5.63, p = 0.012), and high TNM/clinical stage (OR = 2.67, 95%CI = 1.34-5.32, p = 0.005). Additionally, we found that a poor outcome for overall survival (OS) was predicted by an elevation in CASC15 expression (HR = 2.01, 95%CI = 1.71-2.36, p < 0.001). Further investigation of the TCGA dataset revealed that CASC15 had abnormal expression in many cancers, which at least partially validated the findings of the current meta-analysis. According to the latest meta-analysis and systematic review, high expression levels of CASC15 are associated with poor survival outcomes for solid tumor patients, and the use of CASC15 as a solid tumor prognostic predictor has a solid theoretical foundation.

LncRNA CASC15 upregulates cyclin D1 by downregulating miR-365 in laryngeal squamous cell carcinoma to promote cell proliferation

BackgroundThis study investigated the role of lncRNA CASC15 in laryngeal squamous cell carcinoma (LSCC).MethodsThis study included 58 LSCC patients. Both tumor (LSCC) and adjacent (within 3 cm around tumors) non-tumor tissues from 3 different sites of each patient were collected. CCK-8 assay was used to determine cell proliferation. The expression levels of proteins and mRNAs were determined by Western blotting analysis and qRT-PCRs, respectively.ResultsCASC15 was upregulated in LSCC and high expression levels of CASC15 predicted poor survival. In LSCC tissues, CASC15 was negatively correlated with miR-365 but positively correlated with cyclin D1. In LSCC cells, overexpression of CASC15 resulted in downregulation of miR-365 and upregulation of cyclin D1. Overexpression of miR-365 did not affect the expression of CASC15 but downregulated cyclin D1. Overexpression of Cyclin D1 did not affect the expression of miR-365 and CASC15. Overexpression of CASC15 and cyclin D1 led to promoted, while overexpression of miR-365 led to inhibited LSCC cell proliferation. In addition, overexpression of miR-365 reduced the effects of overexpression of CASC15.ConclusionTherefore, CASC15 upregulates cyclin D1 by downregulating miR-365 in LSCC to promote cell proliferation.

Role of LncRNA CASC11 in the malignant transformation of 16HBE cells induced by glycidyl methacrylate

To investigate the effect of trending up-regulation LncRNA CASC11 which is differentially expressed during the malignant transformation of human bronchial epithelial cells(16 HBE) induced by glycidyl methacrylate(GMA). After 16 HBE cells were repeatedly exposed to low concentration GMA(8 μg/mL), the 10 th, 20 th and 30 th passage cells of the GMA group and the DMSO solvent control group were collected. High throughput LncRNA microarray were used to screen the differentially expressed LncRNAs at different stages. Short Time-series Expression Miner and bioinformatics tool RPISeq were used to screen and predict the potential targets of specific LncRNA. Real-time fluorescent quantitative PCR(qPCR) and Western blot were used to detect the relative expression of specific LncRNA and the content of its target protein respectively. The specific differential expression of LncRNA CASC11 in the process of GMA-induced malignant transformation of 16 HBE cells showed a trend of up-regulation. Compared with the control cells in the same period, the P10, P20 and P30 generation cells were down-regulated by 1.64 times, up-regulated by 2.01 times, and up-regulated by 2.66 times, respectively. Western blot showed that the levels of cyclin-dependent kinase 1(CDK1), cyclinB1 and cyclinB2 in P10, P20 and P30 cells after exposure were lower than those in DMSO control group during the same period, which was consistent with the microarray results. The differential expression of LncRNA CASC11 in the process of GMA-induced 16 HBE cell malignant transformation was up-regulated trendingly. It is speculated that it may block or delay cell cycle progression by inhibiting CDK1.

LncRNA CASC15 Promotes Cerebral Ischemia/Reperfusion Injury via miR-338-3p/ETS1 Axis in Acute Ischemic Stroke.

PurposeAcute ischemic stroke (AIS) is a leading health problem caused by cerebral ischemia/reperfusion (CI/R). This study aimed to unveil the potential clinical value and mechanism of lncRNA CASC15.Patients and MethodsThe expression of CASC15, miR-338-3p was detected by quantitative real-time PCR (qRT-PCR). The correlations between CASC15 and national institutes of health stroke scale (NIHSS) scores or miR-338-3p were evaluated by Pearson correlation. A receiver operating characteristic (ROC) curve was performed to provide the diagnostic value of CASC15. Cell Counting Kit-8 (CCK-8) and flow cytometer were used to detect the condition of cell viability and apoptosis. The levels of interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) assay.ResultsThe expression of CASC15 was increased and the levels of miR-338-3p were decreased in AIS patients. A positive association between CASC15 and NIHSS score and an inverse association between CASC15 and miR-338-3p were revealed by Pearson correlation. CASC15 might discriminate AIS patients from healthy people. Silenced CASC15 exerted neuroprotective roles on cell viability, apoptosis, and inflammation via the miR-338-3p/ETS1 axis.ConclusionCASC15 might act as a potential diagnostic biomarker for AIS patients. CASC15/miR-338-3p/ETS1 axis played an essential role in cell viability, apoptosis, and neuroinflammation.

LncRNA CASC15 promotes the proliferation of papillary thyroid carcinoma cells by regulating the miR-7151–5p/WNT7A axis

Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of human thyroid cancer (TC), including papillary thyroid carcinoma (PTC); PTC is the most common pathological subtype of TC. To date, the expression, function, and mechanism of the lncRNA CASC15 in PTC remain unclear. The present study results showed that CASC15 was overexpressed in PTC tissues compared with normal tissues and acted as a potent oncogene to promote the proliferation and tumorigenesis of PTC cells both in vitro and in vivo. Mechanistic studies demonstrated that CASC15 could serve as an endogenous miRNA sponge to absorb and downregulate miR-7151–5p, thereby preventing the inhibition of WNT7A during PTC progression. Furthermore, the study demonstrated that CASC15 activated the WNT/β‑catenin signaling pathway by upregulating WNT7A in PTC. Taken together, our findings identified CASC15 as a potential diagnostic marker or therapeutic target for PTC progression. Data AvailabilityPlease contact the corresponding author for a data request.

The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2.

BackgroundWe previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2.MethodsWe identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression.ResultsWe found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis.ConclusionOur study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.

Contribution of lncRNA CASC8, CASC11, and PVT1 Genetic Variants to the Susceptibility of Coronary Heart Disease.

The purpose of this study was to explore the relationship between lncRNA CASC8, CASC11, and plasmacytoma variant translocation 1 (PVT1). genetic variants and coronary heart disease (CHD) susceptibility among a Chinese Han population. Five single nucleotide polymorphisms were genotyped by Agena MassARRAY platform among 464 CHD patients and 510 healthy controls. Binary logistic regression models by calculating odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between selected single nucleotide polymorphisms and CHD risk. Multifactor dimensionality reduction analysis was performed to analyze gene-gene interaction. PVT1 rs4410871 (OR = 0.77, P = 0.040) was associated with a reduced risk of CHD occurrence in the Chinese population. CASC11 rs9642880 (OR = 1.49, P = 0.021) was a risk factor for increased CHD susceptibility in subjects over 60 years old, and PVT1 rs4410871 was a protective factor for CHD susceptibility in males (OR = 0.67, P = 0.015) and smokers (OR = 0.62, P = 0.047). Complications (hypertension or diabetes) of CHD influenced the association between CASC8, CASC11, and PVT1 genetic polymorphisms and CHD predisposition. Moreover, CASC8, CASC11, and PVT1 polymorphisms were related to the number of pathological branches and Gensini score in CHD patients. The study displayed the contribution of CASC8, CASC11, and PVT1 genetic polymorphisms to CHD predisposition, and these variants could serve as potential biomarkers of CHD susceptibility. These findings contribute to enhancing the understanding of the role of lncRNA polymorphisms in CHD risk.

CASC15: A Tumor-Associated Long Non-Coding RNA.

CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. The relationship between CASC15 and tumors was analyzed by searching references, and summarized the specific pathophysiological mechanism of CASC15. LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma and nasopharyngeal carcinoma. However, CASC15 has been found to be down-expressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

Up-regulation of plasma lncRNA CACS15 distinguished early-stage oral squamous cell carcinoma patient.

To study the role of LncRNA CASC15 in oral squamous cell carcinoma. In the present study, we showed that plasma CASC15 was up-regulated in stage I and II oral squamous cell carcinoma patients than in oral ulcer patients and healthy controls, while no significant correlation was found between oral ulcer patients and healthy controls. Up-regulation of plasma CASC15 distinguished oral squamous cell carcinoma patients from oral ulcer patients and healthy controls. LncRNA MEG3 was inversely correlated with CASC15 in oral squamous cell carcinoma tissues. In oral squamous cell carcinoma cells, CASC15 over-expression led to the inhibited expression of MEG3, and MEG3 over-expression did not alter CASC15 expression. MEG3 over-expression decreased, while CASC15 over-expression increased the proliferation rate of oral squamous cell carcinoma cells. In addition, MEG3 over-expression attenuated the effects of CASC15 over-expression. Therefore, CASC15 over-expression may serve as a potential diagnostic biomarker for oral squamous cell carcinoma, and CASC15 may promote oral squamous cell carcinoma cell proliferation by down-regulating MEG3.

LncRNA CASC15 promotes migration and invasion in prostate cancer via targeting miR-200a-3p.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA CASC15 promotes migration and invasion in prostate cancer via targeting miR-200a-3p, by C. Zhang, G.-X. Wang, B. Fu, X.-C. Zhou, Y. Li, Y.-Y. Li, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8303-8309-DOI:10.26355/eurrev_201910_19141-PMID: 31646560" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19141.

LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA CASC15 functions as an oncogene by sponging miR-130b-3p in bladder cancer, by X. Yu, Z.-L. Wang, C.-L. Han, M.-W. Wang, Y. Jin, X.-B. Jin, Q.-H. Xia, published in Eur Rev Med Pharmacol Sci 2019; 23 (22): 9814-9820-DOI: 10.26355/eurrev_201911_19544-PMID 31799648" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19544.