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BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC).MethodsWe first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression.ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.

Aim: It was aimed to investigate the effect of miR-34a-5p and miR-145-5p on breast cancer cell line MDA-MB-231 and to determine the expressionof target genes of these microRNAs (miRNAs).Materials and Methods: Firstly, literature search and in silico analysis were performed to detect possible target genes of miR-34a-5p and miR-145-5p, which are known to be tumor suppressors. Mimic miR-34a-5p and miR-145-5p were transfected to the breast cancer cell line MDA-MB-231.Deregulated genes were investigated by the quantitative real-time polymerase chain reaction compared to control cells. Also, the effect of thesemiRNAs on proliferation was determined using the Water Soluble Tetrazolium Salt-8 method. Finally, the expressions of epithelial mesenchymaltransition (EMT) markers, which are known to be important in the metastatic process, are examined.Results: The proliferation of the miR-34a-5p or miR-145-5p transfected cells decreased compared to the control groups. The expression of E2Ftranscription factor 1 (E2F1) (p=0.009), mitogen activated protein kinase 1 (MEK1) (p=0.001) and cyclin dependent kinase 4 (CDK4) (p=0.005)genes, which were among the genes targeted by miR-34a-5p, were significantly reduced. EMT markers were significantly changed in miR-34a-5ptransfected cells (E-Cad increase p=0.01; Vimentin decrease p=0.008). Kruppel-like factor 4 (KLF4) (p=0.007) targeted miR-145-5p were significantlyreduced and EMT markers were significantly changed in miR-145-5p transfected cells (E-Cad increase p=0.0005; Vimentin decrease p=0.006).Conclusion: miR-34a-5p and miR-145-5p may have an impact on the breast cancer cell line MDA-MB-231 proliferation and EMT mechanism. Atthe same time, according to our study results, it was revealed that E2F1, MEK1 and CDK4 genes, whose expression level decreased after transfectionof mimic miR-34a-5p, could be targeted by miR-34a-5p in breast cancer, and that the expression level of KLF4, which decreased as a result of mimicmiR-145-5p transfection, could be the target.

Objectives: This study aims to investigate the association between hsa_circ_0037897 and essential hypertension (EH) and to evaluate the diagnostic value of biomarker hsa_circ_0037897 in EH. Methods...

Background: The bone is the most common site of distant metastasis in prostate cancer. However, treatments for the bone metastasis of prostate cancer remain unsatisfactory. MicroRNAs (miRNAs) are small noncoding RNAs that play a variety of critical roles in tumor development and progression. Studies have confirmed that miRNA mimics could regulate the response to therapy in many cancers. Methods: In this study, a set of forty-four miRNAs were reduced in prostate cancer patients with bone metastases by high-throughput sequencing analysis. Wound healing, transwell assays and western blotting analysis were used to explore the role of miRNA mimic in prostate cancer bone metastasis. Results: Further gene ontology and pathway analysis showed that these miRNAs target genes are mainly involved in cellular metabolic process, intracellular membrane-bounded organelle, as well as proteoglycans in cancer and focal adhesion. Therefore, these down-regulated miRNAs may play a key role for prostate cancer bone metastasis treatment, including hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-133a-3p, hsa-miR-222-5p, hsa-miR-204-3p, hsa-miR-145-5p, hsa-miR-3681-5p, hsa-miR-184, hsa-miR-144-3p, hsa-miR-204-5p, and hsa-miR-221-5p. To further investigate the role of these miRNA mimics on prostate cancer bone metastasis, miR-145-5p was randomly selected for validation. Bioinformatics analysis showed that miR-145-5p target genes significantly affected TGF-beta and adherens junction signaling pathway. Wound healing and transwell assays and western blotting analysis revealed that miR-145-5p mimic inhibited proliferation, migration and invasion. Importantly, miR-145-5p mimic increased the expression of E-cadherin and reduced the expression of matrix metalloproteinase 2 and 9. These results revealed that miR-145-5p mimic mediated epithelial mesenchymal transition. Meanwhile, miR-145-5p mimic enhanced the level of caspase 9, which is an important promoter of apoptosis. Conclusions: These results indicate that miR-145-5p mimic could inhibit the progress of prostate cancer bone metastasis via regulation of epithelial mesenchymal transition. In addition, miR-145-5p mimic could induce the apoptosis of prostate cancer cells with bone metastases. In summary, the miR-145-5p mimic is expected to become a novel strategy for the treatment of tumor metastasis.

Background: The Gleason grading system is a major tool used for prediction of prostate cancer (PCa) behavior. Because of heterogeneity and sampling errors, prognosis is variable even among patients with the same Gleason score (GS). Therefore, more accurate biomarkers that complement the Gleason system are needed to improve the clinical management of PCa.Methods: Formalin-fixed, paraffin embedded tissue samples were obtained from radical prostatectomy (RP) (patient set 1, n=53) and needle biopsy (patient set 2, n=107; patient set 3, n=119). Cancer tissues from pure regions of each Gleason pattern (GP) were separately collected using laser-captured microdissection, followed by Real-time-PCR to determine the relative expression of miRNAs, including miR-1-5p, miR-21-5p, miR-30d-5p, miR-100-5p, miR-145-5p, miR-224-5p, and miR-708-5p. miRNA’s association with Gleason upgrading (GU) was evaluated using receiver operator characteristics (ROC) curve and multivariate logistic regression analysis. The integrated miRNA targets prediction and enrichment analyses were performed to determine the potential functions of miRNA. Results: It was found that miR-145-5p in GP3 from radical prostatectomy (RP) were overexpressed in patients with GS6 PCa compared with GS7 patients, which was further confirmed in a larger biopsy cohort. ROC curve analysis revealed that miR-145-5p in biopsy was significantly associated with GU upon RP. In multivariate analyses, miR-145-5p was an independent predictor of GU. Conclusions: Our study indicated that differential expression of miRNAs existed in GP3 from pure GS6 and GS7 PCa, highlighting a path toward the clinical use of miRNAs in predicting GU and assisting in treatment modality selection.

Junchuang He, Hongxian Yan, Sidong Wei, Guoyong Chen Department of Hepatobiliary Pancreatic Surgery, Henan Province People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, 45003, Henan, People’s Republic of ChinaCorrespondence: Junchuang HeDepartment of Hepatobiliary Pancreatic Surgery, Henan Province People’s Hospital, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, Henan, People’s Republic of ChinaTel +86 18838097156Email junchuanghe@163.comBackground: The tumor-promoting roles of ST8SIA6-AS1 and miR-145-5p have been found in several cancers, but their function in cholangiocarcinoma (CHOL) remains speculative. The purpose of this study was to examine the regulatory functions of the ST8SIA6-AS1/MAL2/miR-145-5p pathway in CHOL progression.Methods: RT-qPCR assay was used to detect ST8SIA6-AS1 expression in CHOL tissues and cell lines. Cell migration, apoptosis, invasion, and proliferation abilities were assessed by RIP, RNA pull-down, and luciferase assays. CCK-8, BrdU, transwell, and FITC assays to investigate the regulatory functions of ST8SIA6-AS1, miR-145-5p, and MAL2 function in CHOL cells.Results: Findings revealed the enrichment of ST8SIA6-AS1 in CHOL tissues and cell lines. It was also found that ST8SIA6-AS1 facilitated cell growth and migration, but it reduced the apoptosis level of the CHOL cells. The results of experiments showed that ST8SIA6-AS1 sponged miR-145-5p, thereby allowing MAL2 to exert its biological function on CHOL cells.Conclusion: This research suggested that the ST8SIA6-AS1/miR-145-5p/MAL2 axis could enhance CHOL progression, which might be useful to improve the clinical outcomes of CHOL patients.Keywords: ST8SIA6-AS1, miR-145-5p, MAL2, cholangiocarcinoma, proliferation, apoptosis, migration

Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 μg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1β, IL-6, IL-8 and TNF-α evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-κB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-κB and JNK pathways. Highlights Geniposide prevents LPS-induced injury in PC12 cells; Geniposide up-regulates miR-145-5p; Geniposide protects PC12 cells via up-regulation of miR-145-5p; Geniposide inhibits NF-κB and JNK pathways via up-regulation of miR-145-5p.

IntroductionThis study aimed to investigate the preventive and therapeutic effects of crocetin (Cro) on ischaemic stroke in cell and animal models.Material and methodsA cell model of oxygen and glucose deprivation (OGD) and a rat model of middle cerebral artery occlusion were established to simulate ischaemic stroke. The infarct volume was measured by TTC assay, and the apoptotic cell number was counted by TUNEL. Relative protein and gene expression levels in the rats were measured by immunohistochemical and RT-qPCR assays. The apoptosis rate and relative protein and gene expression levels were determined by flow cytometry, WB and RT-qPCR assay, respectively.ResultsCompared with those in the normal control (NC) group, the brain tissue injury and apoptotic cell number significantly increased (p < 0.001) and the miR-145-5p gene expression significantly decreased in the cell and animal experiments. In the animal experiment, the infarct volume, apoptotic cell number and pathological status improved in the Cro-treated groups. In the cell experiment, the apoptosis rates significantly depressed in the Cro-treated groups (p < 0.05). However, the cell apoptosis rate significantly increased after miR-145-5p inhibitor transfection (p < 0.001). The protein and gene expression levels of Toll-like receptor 4, myeloid differentiation factor 88 and nuclear factor (NF)-κB (p65) significantly decreased (p < 0.05). In addition, p-NF-κB(p65) nuclear volume significantly decreased (p < 0.05).ConclusionsCrocetin improved ischaemic stroke by regulating the miR145-5p/TLR4 axis in cell and animal experiments.

Wang K, Zhao Y, Wang YM. Cancer Management and Research. 2020;12:11359–11369 The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised over the flow cytometry maps and western blot data presented in this article. There also appeared to be errors in the tumor size numbers (n = 108) reported in Table 1, where the subgroups of High and Low MALATI expression do not add up to 54 as reported. The authors responded to our queries but were unable to provide the original raw data for their study and have therefore agreed to retract the article. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Recent evidence reveals that miRNA sponges neutralize miRNAs activity by binding to miRNAs and sequester them from their relevant targets to regulate expression. The detailed mechanisms of sponge RNAs in colorectal cancer remain to be exactly determined. In this study DANCR, miR-145-5p, NRAS axis was evaluated and the diagnostic value of these targets was assessed in colorectal cancer patients. A case-control study was carried out on 40 samples of tumor tissues and 40 adjacent tissues. Total RNA was extracted, and then, the expression level of DANCR, miR-145-5p and NRAS was evaluated using qRT-PCR. In addition, the sensitivity and specificity of these markers were evaluated by receiver operating characteristic (ROC) curve analysis. Our results revealed that the expression level of DANCR was significantly upregulated in colorectal cancer tissues (p

Background: CircRNA is a new type of non-coding RNA that has attracted much attention for involvement in the development and progression of various human diseases, especially cancer. The most reported role of circRNA in many tumors is ‘MiRNA sponge’. We aimed to investigate the role of circBVES in the proliferation and glycolysis of gastric cancer cells and its molecular mechanisms.Methods: In this study, higher CircBVES expression in gastric cancer tissues was detected by RNA sequencing. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of CircBVES in gastric cancer tissues, and the relationship between the expression of CircBVES and prognosis was further analyzed. Then, the effects of CircBVES on the growth and glycolysis of gastric cancer cells were investigated through in vitro and in vivo functional experiments. The interaction between CircBVES and miR-145-5p was detected by bioinformatics analysis, luciferase activity assay and RNA immunoprecipitation.Results: We found that the expression of CircBVES in gastric cancer tissues was evidently up-regulated, and its level was closely correlated with the prognosis of patients with gastric cancer. Inhibition of CircBVES decreased cell proliferation and glycolysis in vitro. Low expression of CircBVES inhibited tumor growth in vivo. Mechanism analysis showed that CircBVES may serve as a competitive endogenous RNA of miR-145-5p to reduce the expression of miR-145-5p in gastric cancer cells, and relieve the repressive effect of miR-145-5p on target genes HMGB3 and cycle-related proteins CCNE1 and CDK2.Conclusions: Our results suggest that CircAGFG1 may promote the progress of gastric cancer through the CircBVES / miR-145-5p / HMGB3 axis, providing a new target for the treatment of gastric cancer cells.

Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.

In the light of emerging global epidemics of type 2 diabetes mellitus significant efforts are continuing to discover novel biomarkers for early detection of the disease. Since miRNAs play an important role in both the initiation and progress of many pathologic processes such as diabetes, in this study we aimed to evaluate expression level of plasma miR-145-5p in diabetics and pre-diabetics in comparison to the control group and assess its use as a biomarker in diagnosis of T2D. The plasma level of miR-145-5p was assessed in three groups including 20 prediabetic patients, 20 T2D patients and 20 healthy controls using RT-qPCR. Biochemical parameters were also measured by the auto-analyzer. Expression level of miR-145-5p was down-regulated in the prediabetics and the T2D patients compared to the controls. In the control group miR-145-5p showed a borderline correlation with FBS (

An increasing number of studies have demonstrated that circular RNAs (circRNAs), as promising therapeutic targets, are essential for diverse human diseases, especially cancer. However, the potential functions and complex mechanisms of most circRNAs in osteosarcoma (OS) are still not fully elucidated. In the present study, we obtained the expression profile of circRNAs from a GEO database (GSE96964) and identified hsa_circ_0000073 as a highly expressed candidate in OS. Overexpression of hsa_circ_0000073 accelerated the proliferation, migration, invasion and MTX resistance of OS cells, and knockdown of hsa_circ_0000073 resulted in the opposite effects. Mechanistically, hsa_circ_0000073 upregulated NRAS expression by targeting miR-145-5p and miR-151-3p in OS cells. In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.

Shengting Wang,1 Xukai Xue,2 Rui Wang,1 Xiaoming Li,1 Qian Li,1 Yufang Wang,1 Peijun Xie,1 Yuhua Kang,1 Rui Meng,1 Xinghua Feng1 1Department of Clinical Medicine, Peihua University, Xi’an 710125, China; 2Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an 710054, China Background: Accumulating evidence suggests that circular RNAs (circRNAs) play critical roles in carcinomas. However, the contributions of circRNAs to breast cancer remain unclear. Herein, we determined the role of circZNF609 in breast cancer.Methods: A total of 143 breast cancer and 38 normal tissues were collected to assess the expression of circZNF609 and its relationship with breast cancer prognosis. A series of in vitro and in vivo functional experiments were carried out to elucidate the role of circZNF609 in breast cancer progression and its underlying molecular mechanisms.Results: CircZNF609 was markedly over-expressed in breast cancer tissues and cell lines, and high circZNF609 expression was closely associated with poor outcome. Silencing of circZNF609 inhibited the malignant phenotype of breast cancer in vitro and in vivo. Mechanistically, circZNF609 served as a sponge of miR-145-5p to elevate p70S6K1 expression. Moreover, miR-145-5p overexpression or p70S6K1 knockdown abrogated the oncogenic effects of circZNF609 in breast cancer. In addition, clinically, a strong negative correlation was observed between the expression of circZNF609 and miR-145-5p in breast cancer tissues (r=–0.597, P

Age-related macular degeneration (AMD), mainly wet AMD, is the major reason for nonreversible vision loss worldwide. Choroidal neovascularization (CNV) is a characteristic pathological manifestation of wet AMD. Stress or injury to the retinal pigment epithelium (RPE) induces proangiogenic factors that drive CNV. An iridoid glycoside extracted from the fruit of gardenia, geniposide (GEN) plays an antiangiogenic role. In this study, GEN inhibited the transcription and expression of heparin-binding epidermal growth factor (HB-EGF), a proangiogenic factor, in hypoxic RPE cells and a mouse laser-induced CNV model. Inhibition of glucagon-like peptide-1 receptor (GLP-1R), a GEN receptor blocker, eliminated the protective effect of GEN. Additionally, GEN decreased the transcription and expression of HB-EGF in hypoxia-exposed RPE cells by downregulating the miR-145-5p/NF-κB axis. Therefore, our research provides a promising novel strategy for wet AMD therapy.

The present study was aimed to evaluate the isoxanthanol against Staphylococcus aureus chronic obstructive pulmonary disease (COPD) in rat model. The isoxanthanol decreased the parasitic load by almost 99% in the Staphylococcus aureus infected rats. It significantly (P 0.05) decreased mortality rate of the rats, prevented pulmonary tissue damage and aggregation of inflammatory cytokines. In Staphylococcus aureus infected rats, isoxanthanol treatment inhibited production of interleukin-18, interleukin-1β and TNF-α significantly (P 0.05) in the BALF and pulmonary tissues. Treatment of the Staphylococcus aureus-infected rats with isoxanthanol inhibited up-regulation of NLRP3, ASC and caspase-1 expression. In Staphylococcus aureus-infected rats the expression of miR-145-5p was remarkably increased on treatment with isoxanthanol. In summary, isoxanthanol prevents Staphylococcus aureus-induced COPD in rats through up-regulation of miR-145-5p and suppression of inflammatory cytokines. Therefore, isoxanthanol can be of therapeutic importance for the treatment of Staphylococcus aureus induced COPD.

Long non-coding RNA (LncRNA) BRE-AS1 has recently proven to be a tumor suppressor in lung cancer. The present study aimed to investigate the involvement of lncRNA BRE-AS1 in prostate carcinoma (PC). In the present study we found that plasma BRE-AS1 and miR-145-5p were both down-regulated in PC patients than in healthy controls. Down-regulation of BRE-AS1 and miR-145-5p effectively distinguished early-stage PC patients from healthy controls. A significant and positive correlation between BRE-AS1 and miR-145–5p was only found in PC patients. BRE-AS1 overexpression mediated miR-145-5p up-regulation in PC cells, while miR-145-5p overexpression did not significantly affect BRE-AS1. Overexpression of BRE-AS1 and miR-145-5p led to inhibited proliferation and promoted apoptosis of PC cells. miR-145-5p inhibitor attenuated the effects of BRE-AS1 overexpression on cancer cell behaviors. Therefore, lncRNA BRE-AS1 may regulate cancer cell proliferation and apoptosis in PC by interacting with miR-145-5p.

Background Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. Materials and methods TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). Results The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients—miR-145-5p (P = 6.5e−12), miR-191-5p (P = 3.7e−10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. Conclusions Two plasma miRNAs—miR-145-5p and miR-191-5p—are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.

MicroRNAs have been reported to be involved in various biological processes. Here, we performed a systematic analysis to explore the clinical value and potential molecular mechanism of miR-145-5p in non-small cell lung cancer. First, a meta-analysis was performed with eligible literature, followed by microRNA microarrays in the Gene Expression Omnibus database, to verify the diagnostic and prognostic values of miR-145-5p. A cohort of 125 clinical paired non-small cell lung cancer samples was next used to detect the level of miR-145-5p and to explore the relationship of miR-145-5p with clinicopathological parameters. The Cancer Genome Atlas database was additionally applied to investigate the role of miR-145-5p in non-small cell lung cancer. The potential targets of miR-145-5p were predicted using 12 online prediction databases to explore the prospective molecular mechanism of miR-145-5p in non-small cell lung cancer. The expression of miR-145-5p in non-small cell lung cancer was significantly lower than that in healthy tissues. And miR-145-5p tended to show better diagnostic performance in lung squamous cell carcinoma than in lung adenocarcinoma. Furthermore, the expression of miR-145-5p was closely associated with lymph node metastasis in non-small cell lung cancer. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes were mainly enriched with enzyme-linked receptor protein signaling pathways, SH3 domain binding, cell leading edge, and adherens junction. The protein–protein interaction network showed that eight hub genes (SMAD4, SMAD2, IRS1, FOXO1, ERBB4, NRAS, ACTB, and ACTG1) might be the key target genes of miR-145-5p in non-small cell lung cancer. The information we obtained might offer new perspectives for clinical diagnosis and treatment for non-small cell lung cancer.

The above article from the Journal of Cellular Physiology, published online on 7 December 2017 in Wiley Online Library (wileyonlinelibrary.com), has been withdrawn by agreement between the authors, the journal Editor in Chief, Gary Stein, and Wiley Periodicals, Inc. The withdrawal has been agreed due to the article being submitted for publication without the consent of the authors' instructor.

The rarity and biological variety of thymic malignancies hampers the performance of randomized clinical trials and thus limits the availability for guidelines in treatment decisions.