Aim:To identify serum biomarkers for non-small cell lung cancer(NSCLC)and assess their potential for early diagnosis. Experimental:MB-WCX coupled with MALDI-TOF MS was utilized to profile serum samples from 64 NSCLC patients and 64 healthy subjects,followed by ClinProTools software and Liquid chromatography-electrospray ionization-tandem mass spectrometry(LC-ESI-MS/MS)for recognition and characterization of differentially expressed peaks.Enzyme-linked immunosorbent assay(ELISA)confirmed protein concentrations,while The Cancer Genome Atlas(TCGA)database was leveraged for validation of candidate biomarkers in a larger cohort. Results:39 distinct proteomic m/z peaks were identified for NSCLC subjects,with five of these peaks significantly distinguishing NSCLC from healthy controls(HC).A model developed using the GA(Genetic Algorithm)with ClinProt data demonstrated a sensitivity of 84.72%and a specificity of 88.68%in identifying NSCLC patients.Peaks 2 through 5 were observed to be downregulated in the NSCLC group.Notably,a peptide peak,Peak 1,with an m/z value of 1,866,identified as a fragment of TUBB,was upregulated in NSCLC.ELISA validated the increased serum TUBB levels in NSCLC patients(P<0.001).Furthermore,analysis of TUBB expression in lung cancer tissues through TCGA data revealed elevated TUBB expression in lung cancer tissues. Conclusions:Serum TUBB is identified as a potential diagnostic biomarker for NSCLC,which may benefit early diagnosis and enhance the survival rate of NSCLC patients.

The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

Background Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing TKI resistance may involve targeting the renewal and repopulation of stem-like cells. To investigate the underlying mechanisms, we conducted RNA Microarray and m6A Epi-Transcriptomic Microarray analyses, followed by assessment of transcription factors. Additionally, we specifically designed a tag to detect the polypeptide circRNA-AA, and its expression was confirmed through m6A regulations. Results We initially identified unique molecular signatures present in cancer stem cells that contributed to poor therapeutic responses. Activation of the alternative Wnt pathway was found to sustain the renewal and resistant status of these cells. Through bioinformatics analysis and array studies, we observed a significant decrease in the expression of circFBXW7 in Osimertinib-resistant cell lines. Notably, the abnormal expression pattern of circFBXW7 determined the cellular response to Osimertinib. Functional investigations revealed that circFBXW7 inhibits the renewal of cancer stem cells and resensitizes both resistant LUAD cells and stem cells to Osimertinib. In terms of the underlying mechanism, we discovered that circFBXW7 can be translated into short polypeptides known as circFBXW7-185AA. These polypeptides interact with β-catenin in an m6A-dependent manner. This interaction leads to reduced stability of β-catenin by inducing subsequent ubiquitination, thereby suppressing the activation of canonical Wnt signaling. Additionally, we predicted that the m6A reader, YTHDF3, shares common binding sites with hsa-Let-7d-5p. Enforced expression of Let-7d post-transcriptionally decreases the levels of YTHDF3. The repression of Let-7d by Wnt signaling releases the stimulation of m6A modification by YTHDF3, promoting the translation of circFBXW7-185AA. This creates a positive feedback loop contributing to the cascade of cancer initiation and promotion. Conclusions Our bench study, in vivo experiments, and clinical validation have unequivocally shown that circFBXW7 effectively inhibits the abilities of LUAD stem cells and reverses resistance to TKIs by modulating Wnt pathway functions through the action of circFBXW7-185AA on β-catenin ubiquitination and inhibition. The regulatory role of circRNA in Osimertinib treatment has been rarely reported, and our findings reveal that this process operates under the influence of m6A modification. These results highlight the tremendous potential of this approach in enhancing therapeutic strategies and overcoming resistance to multiple TKI treatments.

Purpose: To determine the effectiveness of neoadjuvant chemotherapy (NACT) versus primary surgery on survival outcomes for resectable non-small-cell lung cancer (NSCLC) using an approach based on a meta-analysis. Methods: The PubMed, EmBase, Cochrane library, and CNKI databases were systematically browsed to identify randomized controlled trials (RCTs) which met a set of predetermined inclusion criteria throughout January 2020. Hazard ratios (HRs) were applied for the pooled overall survival (OS) and progression-free survival (PFS) values, and the pooled survival rates at 1-year and 3-year were used as the relative risk (RR). All the pooled effect estimates with 95% confidence intervals (CIs) were calculated using the random-effects model. Results: Nineteen RCTs contained a total of 4372 NSCLC at I-III stages was selected for final meta-analysis. We noted NACT was significantly associated with an improvement in OS (HR: 0.87; 95%CI: 0.81-0.94; P < 0.001) and PFS (HR: 0.86; 95%CI: 0.78-0.96; P = 0.005). Moreover, the survival rate at 1-year (RR: 1.07; 95%CI: 1.02-1.12; P = 0.007) and 3-year (RR: 1.16; 95%CI: 1.06-1.27; P = 0.001) in the NACT group was significantly higher than the survival rate for the primary surgery group. Finally, the treatment effects of NACT versus primary surgery on survival outcomes might be different when stratified by the mean age of patients and the tumor stages. Conclusions: NACT could improve survival outcomes for patients with resectable NSCLC, suggesting its suitable future applicability for clinical practice. However, large-scale RCT should be conducted to assess the chemotherapy regimen on the prognosis of resectable NSCLC.

BackgroundLung cancer is still the top-ranked cancer-related deaths all over the world. Now immunotherapy has emerged as a promising option for treating lung cancer. Recent evidence indicated that lncRNAs were also key regulators in immune system. We aimed to develop a novel prognostic signature based on the comprehensive analysis of immune-related lncRNAs to predict survival outcome of LUAD patients.MethodsThe gene expression profiles of 491 LUAD patients were downloaded from TCGA. 1047 immune-related lncRNAs were obtained through Pearson correlation analysis of immune genes and lncRNAs using statistical software R language. Univariate and multivariate Cox regression analysis were performed to determine the optimal immune-related lncRNAs prognostic signature (ITGCB-DT, ABALON, TMPO-AS1 and VIM-AS1). Finally, we validated the immune-related lncRNAs prognostic signature in The First Affiliated Hospital of Xi’an Jiaotong University cancer center cohort.ResultsA four immune-related lncRNAs prognostic signature was constructed to predict the survival outcome of LUAD patients. Statistical significance were found that the LUAD patients in high-risk group suffered shorter overall survival than those in low-risk group (P <0.001). ROC curve analysis shown that the four immune-related lncRNAs prognostic signature had the best predictive effect compared with age, gender, AJCC-stage, T stage, N stage, M stage (AUC = 0.756). More importantly, clinical cohort studies proved that the signature could predict the overall survival of LUAD patients with an AUC = 0.714.ConclusionsIn summary, we demonstrated that the novel immune-related lncRNAs signature had the ability to predict the prognosis of LUAD patients, which might serve as potential prognostic biomarkers and guide the individualized treatment strategies for LUAD patients.

目的:探讨术中灭菌注射用水在腹腔冲洗中的用量对腹腔镜微创手术治疗局部进展期食管胃交界部腺癌(AEG)患者疗效的影响.方法:选取2013年10月至2014年12月行腹腔镜手术治疗的进展期AEG患者120例,按照灭菌注射用水在腹腔冲洗中的用量分为4组,每组30例.A组:1000 mL;B组:3000 mL;C组:5000 mL;D组:10000 mL.比较4组患者的手术并发症及不良反应发生率、术后局部复发率、转移率及无进展生存率.结果:4组患者手术并发症的发生率、不良反应发生率未见明显差异(P>0.05).4组患者的肝转移率、1年无进展生存率未见明显差异(P>0.05),A、B组的局部复发率、转移率和无进展生存率无明显差异(P>0.05),C、D组的局部复发率、转移率和无进展生存率无明显差异(P>0.05).但是C、D组的局部复发率和腹腔转移率均低于A、B组,3年及5年无进展生存率均高于A、B组(P<0.05).按照肿瘤浸润深度、有无淋巴结转移分层情况,可见在T2期和无淋巴结转移的患者中,4组的局部复发率、转移率、无进展生存率未见明显差异(P>0.05);而在肿瘤浸润较深的T3或T4a期以及有淋巴结转移的患者中,虽然4组患者的肝转移率、1年无进展生存率未见明显差异(P>0.05),但是C、D组的局部复发率和腹腔转移率均低于A、B组,3年及5年无进展生存率均高于A、B组(P<0.05),而且D组的腹腔转移率还低于C组(P<0.05),3年及5年无进展生存率还高于C组(P<0.05).结论:随着冲洗腹腔的灭菌注射用水的用量增加,能够有效降低患者的局部复发率和腹腔转移率,提高患者的无进展生存率,延长患者的无进展生存期,但是无法降低肝转移发生率,对肿瘤浸润较深、有淋巴结转移的患者,应提倡此手术操作.

目的:对进展期Siewert Ⅱ型食管胃结合部腺癌三种不同术式治疗后患者生活质量进行比较,为优化进展期Siewert Ⅱ型食管胃结合部腺癌患者的手术治疗提供理论依据.方法:选取西安交通大学第一附属医院2015年10月至2017年10月收治的进展期Siewert Ⅱ型食管胃结合部腺癌患者105例.根据术式将患者分为三组,每组35例,分为全胃切除组(A组)、传统近端胃切除组(B组)和双通道吻合组(C组).采用癌症患者总体生活质量量表(quality of life questionnaire core-30,QLQ-C30)、食管胃结合部癌专用量表(quality of life questionnaire oesophagogastric-25,QLQ-OG25)进行量化后,比较上述三组患者术后半年和1年的生活质量差异.结果:QLQ-C30:术后半年:C组在总体生活质量、躯体功能、疲乏及呼吸困难等方面均优于A组和B组(P<0.05),情绪功能优于A组(P<0.05);A组在角色功能、疲乏、腹泻等方面均差于B组和C组(P<0.05);B组的食欲减退症状重于A组及C组(P<0.05).术后1年:C组总体生活质量、躯体功能及情绪功能等方面均优于A组及B组(P<0.05),角色功能优于A组(P<0.05);A组疲乏与腹泻症状均重于B组和C组(P<0.05);B组食欲减退症状重于A组和C组(P<0.05).QLQ-OG25:术后半年:A组在饮食限制、焦虑、腹泻等方面症状均差于B组和C组(P<0.05);B组返流症状重于A组和C组(P<0.05).术后1年:A组的焦虑、腹泻症状均重于B组和C组(P<0.05);B组反流症状重于A组和C组(P<0.05).结论:对于进展期Siewert Ⅱ型食管胃结合部腺癌,采用双通道吻合法的患者术后生活质量优于传统近端胃切除及全胃切除的患者,该术式值得临床推广.

The article, from Journal of Medical Virology, "Anisodamine (654-2) inhibits inflammation to alleviate influenza A virus-induced acute lung injury" by Ning Du, Dapeng Liu, Xin Sun, Sida Qin, Hong Ren, published online on 02 June 2021 in Wiley Online Library (http://wileyonlinelibrary.com) has been withdrawn by agreement with the Journal Editor-in-Chief, Shou-Jiang Gao. The withdrawal has been agreed due to lack of response from author.

The magnetic anchoring lung nodule positioning device is composed of a target magnet, an anchor magnet, a coaxial puncture needle and a puncture navigation template, through these, a new type of accurate positioning technology for small pulmonary nodules is derived. The device inserts the target magnet into the both sides nearby the lung nodule under the guidance of CT. Helped by the mutual attraction of the two target magnets, they can be fixed in the lung tissue, avoiding the movement in the lung, and accurately positioning the target lung nodule before surgery. In thoracoscopic surgery, the anchor magnet and the target magnet attract each other to achieve the purpose of positioning the target nodule. The device uses the characteristics of non-contact suction of magnetic materials biomedical engineering technology, eliminating the previous procedure of direct interaction with the positioning marks, finally achieves the target of precise positioning of lung nodules and rapid surgical removal.

以团队为基础的学习(TBL)教学法是近年来人才培养的新兴教育方法,并得到了广泛应用.其是以问题为导向的教学方法的创新与发展,受到医学教育工作者的认可与应用.本文通过分析TBL的特点,探讨其在国家住院医师规范化培训中应用的优势,以提高规培生在临床工作及学习中的积极性,同时结合目前国家住院医生培养政策下存在的问题,提出TBL教学法应用下的预期成效及存在的问题,以期为我国住院医师的规范化培训添砖加瓦.

目的:探讨胃癌组织中FOXQ1和Snail的表达及其与临床病理特征和预后的关系.方法:采用免疫组织化学方法检测178例胃癌组织中FOXQ1和Snail的表达,比较FOXQ1和Snail的表达与临床病理特征和生存期的关系.结果:在178例胃癌中,FOXQ1和Snail过表达分别为103例(57.8％)和87例(48.9％),76例(42.7％)同时表达FOXQ1和Snail.FOXQ1的表达与胃癌pTNM分期(P＜0.001)、浸润深度(P＜0.001)、淋巴结转移(P＜0.001)、远处转移(P=0.001)、分化程度(P=0.002)和肿瘤直径(P=0.001)有关.Snail的表达与胃癌pTNM分期(P＜0.001)、浸润深度(P＜0.001)、淋巴结转移(P＜0.001)、远处转移(P=0.001)、Borrmann分型(P=0.016)、分化程度(P=0.037)和肿瘤直径(P＜ 0.001)有关.结果表明,FOXQ1高表达与Snail表达呈正相关(r=60.705,P＜0.001).Kaplan-Meier生存分析显示,FOXQ1或Snail表达与OS相关(P＜ 0.001).单因素分析显示FOXQ1、Snail、pTNM分期、浸润深度、淋巴结转移、肿瘤直径分别与5年OS显著相关.多因素COX分析显示,FOXQ1 (HR 2.621,95％CI 1.571-4.374,P＜ 0.001)、Snail(HR 2.925,95％CI 1.767-4.841,P＜0.001)和淋巴结转移(HR1.345,95％CI 1.130-1.601,P=0.001)是胃癌的独立预后因素.结论:FOXQ1与Snail的表达密切相关,FOXQ1与Snail的联合表达模式可作为胃癌患者更有效的预后指标.FOXQ1与Snail在胃癌上皮间质转化过程中的确切作用机制有待进一步研究.

The aim of this study was to identify a novel cancer stemness-related ceRNA regulatory axis in lung adenocarcinoma (LUAD) via weighted gene coexpression network analysis of a stemness index. The RNA sequencing expression profiles of 513 cancer samples and 60 normal samples were obtained from the TCGA database. Differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) were identified with R software. Functional enrichment analysis was conducted using DAVID 6.8. The ceRNA network was constructed via multiple bioinformatics analyses, and the correlations between possible ceRNAs and prognosis were analyzed using KaplanMeier plots. WGCNA was then applied to distinguish key genes related to the mRNA expression-based stemness index (mRNAsi) in LUAD. After combining the weighted gene coexpression and ceRNA networks, a novel ceRNA regulatory axis was identified, and its biological functions were explored in vitro and vivo. In total, 1,825 DElncRNAs, 291 DEmiRNAs, and 3,742 DEmRNAs were identified. Functional enrichment analysis revealed that the DEmRNAs might be associated with LUAD onset and progression. The ceRNA network was constructed with 14 lncRNAs, 10 miRNAs, and 52 mRNAs. KaplanMeier analysis identified 2 DEmiRNAs, 5 DElncRNAs, and 41 DEmRNAs with remarkable prognostic power. One gene (MFAP4) in the ceRNA network was found to be closely related to mRNAsi by using WGCNA. Functional investigation further confirmed that the C8orf34-as1/miR-671-5p/MFAP4 regulatory axis has important functions in LUAD cell migration and stemness. This study provides a deeper understanding of the lncRNAmiRNAmRNA ceRNA network and, more importantly, reveals a novel ceRNA regulatory axis, which may provide new insights into novel molecular therapeutic targets for inhibiting LUAD stem characteristics.

BACKGROUND:Smac mimetics are a type of drug that can induce apoptosis by antagonizing IAP family members in cancer treatment. However, a recent study showed that Smac mimetics can trigger cell invasion and migration in cancer cells by activating the NF-κB pathway.METHODS:We assessed lung cancer cell elongation, invasion and migration under treatment with the Smac mimetic LCL161. Functional analyses (in vitro and in vivo) were performed to detect the contribution of NIK and OTUD7B to LCL161-induced cell invasion and migration. The role of OTUD7B in regulation of the TRAF3/NIK/NF-κB pathway under LCL161 treatment was analysed by immunoblotting, immunoprecipitation, luciferase and ubiquitin assays, shRNA silencing and plasmid overexpression. Expression levels of OTUD7B, NIK and TRAF3 in tissue samples from lung cancer patients were examined by immunohistochemistry.RESULTS:We found that LCL161 stimulates lung cancer cell elongation, invasion and migration at non-toxic concentrations. Mechanistically, LCL161 results in NIK accumulation and activates the non-canonical rather than the canonical NF-κB pathway to enhance the transcription of target genes, such as IL-2 and MMP-9. Importantly, knockdown of NIK dramatically suppresses LCL161-induced cell invasion and migration by reducing the proteolytic processing of p100 to p52 and target gene transcription. Interestingly, we discovered that OTUD7B increases TRAF3 and decreases NIK to inhibit the non-canonical NF-κB pathway and that overexpression of OTUD7B suppresses LCL161-induced cell invasion and migration. Notably, OTUD7B directly binds to TRAF3 rather than to NIK and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing NIK accumulation and NF-κB pathway activation. Furthermore, the OTU domain of OTUD7B is required for the inhibition of LCL161-induced cell invasion and migration, as demonstrated by transfection of the C194S/H358R(CH) mutant OTUD7B. Finally, we investigated whether OTUD7B inhibits LCL161-induced lung cancer cell intrapulmonary metastasis in vivo, and our analysis of clinical samples was consistent with the above findings.CONCLUSIONS:Our study highlights the importance of OTUD7B in the suppression of LCL161-induced lung cancer cell invasion and migration, and the results are meaningful for selecting lung cancer patients suitable for LCL161 treatment.

目的:研究miR-367-3p在非小细胞肺癌(non-small cell lung cancer,NSCLC)中促进肿瘤生长的作用机制.方法:收集非小细胞肺癌患者的临床标本,检测miR-367-3p在非小细胞肺癌组织中的表达.利用qRT-PCR、MrTT和流式细胞术分别评估miR-367-3p的表达改变对肿瘤细胞增殖和周期的影响.Western blot检测miR-367-3p表达改变对FBXW7的影响.双荧光素酶实验验证miR-367-3p与FBXW7之间的直接关系.结果:miR-367-3p在非小细胞肺癌组织中的表达明显高于对应癌旁组织.miR-367-3p作为促癌的miRNA,在非小细胞肺癌细胞中促进肿瘤细胞增殖和细胞周期进程.miR-367-3p对NSCLC细胞生物学功能的影响部分依赖靶向抑制FBXW7.结论:miR-367-3p通过靶向抑制FBXW7的表达促进NSCLC细胞增殖和周期.

The aim of this study was to investigate the potential biological activities of nutlin-3 in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC) stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. Nutlin-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with nutlin-3 and then treated with either an Akt1 activator or shRNA-GSK3β, to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels of GSK3β and p-Akt1 in patients with NSCLC and determined their potential association with survival data using Kaplan‐Meier plots and CBIOTAL. Increased p53 expression stimulated the induction of apoptosis by axitinib and promoted asymmetric cell division (ACD) of NSCLC CSCs. The repression of Akt phosphorylation induced by nutlin-3 promoted the ACD of lung CSCs, decreasing the proportion of the stem cell population. In addition to the induction of apoptosis by axitinib through inhibition of Wnt signaling, nutlin-3 treatment further enhanced axitinib-induced apoptosis by inhibiting Akt1/GSK3β/Wnt signaling. The low expression of GSK3β and increased expression of p-Akt in patients with NSCLC were closely associated with the development of NSCLC. TP53 stimulates the induction of apoptosis in NSCLC by axitinib and the ACD of lung CSCs through its regulatory effects on the p53/Akt/GSK3β pathways.

Objective:TostudytheroleofFBXW7inepithelial－mesenchymaltransformationofnon－smallcell

BackgroundThe differences in gastric cancer between East and West have been frequently discussed. However, there are few studies that have compared Japan and China in Asia.MethodsPatient characteristics, surgical procedures and pathologic information were compared among gastric cancer patients who underwent curative-intent gastrectomy at two large volume cancer centers in China and Japan.ResultsThe median age of Japanese patients is 70 years, seven years older than those in China, and more than 25% of Japanese patients were older than 75. In China, the tumor was thicker, and lymph node metastasis was frequently observed. Total gastrectomy was more common in China (35.6% vs 21.9%). Distal gastrectomy rate was 56.0 percent in Japan, compared to 42.2 percent in China. The proportion of patients undergoing proximal gastrectomy was almost equal in China and Japan. Further analysis of the characteristics of patients undergoing total gastrectomy revealed that in China, more advanced gastric cancer patients with larger tumors and more lymph node metastasis underwent total gastrectomy, while in Japan, more early stage gastric cancer patients underwent total gastrectomy.ConclusionThere are some differences in gastric cancer between Japan and China. China needs to learn from Japan by establishing some screening programs for the diagnosis and treatment of early gastric cancer.

Accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play pivotal roles in the processes of cancer occurrence, progression, and treatment. FAM83A-AS1 is a novel onco-lncRNA involved in various cancers. Nevertheless, the biological function and underlying mechanism of FAM83A-AS1 in lung adenocarcinoma (LUAD) remain largely unclear. In this study, we found FAM83A-AS1 to be upregulated in LUAD tissues and closely associated with tumor size, lymph node metastasis, and TNM stage. In addition, high FAM83A-AS1 expression correlated positively with a poor prognosis. Functional investigation revealed that FAM83A-AS1 promotes LUAD cell proliferation, migration, invasion and the epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Mechanistically, FAM83A-AS1 functions as an endogenous sponge of miR-150-5p by directly targeting it, removing inhibition of MMP14, a target of miR-150-5p. Furthermore, rescue assays demonstrated that FAM83A-AS1 enhances cell migration, invasion and EMT by modulating the miR-150-5p/MMP14 pathway. Collectively, we conclude that the novel FAM83A-AS1/miR-150-5p/MMP14 axis regulates LUAD progression, suggesting an innovative therapeutic strategy for this cancer.

Objective:To investigate the role of Hedgehog signaling pathway in the effect of Let-7a inhibition of triple-negative breast cancer.Methods: MTT assay and flow cytometry were used to detect the effect of Hedgehog pathway on apoptosis of breast cancer cells induced by Let-7a.Western blot analysis,luc-assay experiments were used to verify the changes in the downstream signaling pathways associated with Let-7a caused by the Hedgehog signaling pathway.Immunofluorescence assay was used to detect the effect of Hedgehog pathway inhibitor on the phenotypic changes of breast cancer stem cells caused by Let-7a.Immunohistochemistry was used to detect the expression of Hedgehog pathway-activated downstream molecules related with Let-7a in different stages of breast cancer tissues.Results:The inhibition of Hedgehog alone inhibited the proliferation of MDA-MB-231 cells and BT-20 cells,and helps to sensitize MDA-MB-231 and BT-20 cells to Let-7 induced proliferation inhibition.Let-7 did not influence the Cyclin D1 level significantly in TNBC cells,but its effects were strengthened by Hedgehog pathway inhibitor,and the effects were identified by Western blot,luc-assay and immunofluorescence.Cyclopamine inhibited the ALDH1 (+) cells of both MDA-MB-231 and BT-20 cells,and increased the inhibitory effects of Let-7 on suppressing the self-renewal ability of TNBC cells.Conclusion: Hedgehog inhibitor may be used to improve the tumor supression response caused by Let-7 miRNAs in triple negative breast cancer.

Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a poor prognosis. The microRNA‐200 (miR‐200) family has been associated with breast cancer metastasis. However, the epigenetic mechanisms underlying miR‐200b repression in TNBC are not fully elucidated. In this study, we found that MYC proto‐oncogene, bHLH transcription factor (MYC) and DNA methyltransferase 3A (DNMT3A) were highly expressed in TNBC tissues compared with other breast cancer subtypes, while miR‐200b expression was inhibited significantly. We demonstrated that MYC physically interacted with DNMT3A in MDA‐MB‐231 cells. Furthermore, we demonstrated that MYC recruited DNMT3A to the miR‐200b promoter, resulting in proximal CpG island hypermethylation and subsequent miR‐200b repression. MiR‐200b directly inhibited DNMT3A expression and formed a feedback loop in TNBC cells. MiR‐200b overexpression synergistically repressed target genes including zinc‐finger E‐box‐binding homeobox factor 1, Sex determining region Y‐box 2 (SOX2), and CD133, and inhibited the migration, invasion and mammosphere formation of TNBC cells. Our findings reveal that MYC can collaborate with DNMT3A on inducing promoter methylation and miR‐200b silencing, and thereby promotes the epithelial to mesenchymal transition and mammosphere formation of TNBC cells.