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Background Metastasis and drug resistance of breast cancer have become a barrier to treating patients successfully. Long noncoding RNAs (lncRNAs) are known as vital players in cancer development and progression. Methods The RT-qPCR were used to detect the gene expression. Colony formation assay, would healing assay, and transwell assay were performed to investigate oncogenic functions of cells. CCK8 assay was used to detect the cell vability. Western blot was applied to detect the protein level. Dual-luciferase reporter assay was used to determine the relationship between molecules. Mouse orthotopic xenograft tumor models were established to evaluate the effects of BCAR4 on tumor growth and metastasis in vivo. Results LncRNA BCAR4 was significantly increased in breast cancer patients’ tissues and plasma and upregulated in breast cancer cell lines. BCAR4 upregulation was correlated with the TNM stages and decreased after surgical removal of breast tumors. Silencing of BCAR4 suppressed breast cancer cell colony formation, migration, invasion, and xenograft tumor growth and promoted chemo-sensitivity. Mechanistically, BCAR4 facilitates breast cancer migration and invasion via the miR-644a-CCR7 axis of the MAPK pathway. BCAR4 promotes ABCB1 expression indirectly by binding to and down-regulating miR-644a to induce chemo-resistance in breast cancer. Conclusions Our findings provide insights into the oncogenic role of BCAR4 and implicate BCAR4 as a potential diagnostic biomarker and a promising therapeutic agent to suppress metastasis and inhibit chemo-resistance of breast cancer.

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

Pancreatic cancer is one of the most lethal digestive malignant tumors. We had previously found that microRNA-301a (miR-301a) is a oncogenic microRNA whose recognized conduce to nuclear factor-kappa B (NF-κB) activation in pancreatic cancer, yet the underlying mechanisms of miR-301a in promoting pancreatic cancer invasion and migration is obscure. In this work we found that high expression of miR-301a in human pancreatic cancer patients is related to poor survival. Overexpression of miR-301a enhances pancreatic cancer cell invasion, angiogenesis and migration, whereas inhibition of miR-301a suppresses pancreatic cancer cell invasion and reduces orthotopic pancreatic tumor growth and metastasis. Furthermore, suppressor of cytokine signaling 5 (SOCS5) is identified as a target gene of miR-301a. We found that miR-301a suppressed the expression of SOCS5 leads to janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) activation and is related to poor overall survival of pancreatic cancer patients. Taken together, our data show for the first time that the feedback loop between miR-301a and JAK/STAT3 pathway may play a significant role in pancreatic cancer invasion and metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for pancreatic cancer.

Additional file 1: Table S1. Univariate logistic regression analysis of serum CPT1A and lipids in differentiating breast cancer and controls. Table S2. Formulas of logistic regression models built based on the data in the training set. Table S3. The reference ranges of serum tumor markers and lipids. Figure S1. Merged original blot showing CPT1A and β-Actin bands with protein markers in a panel of non-malignant cell lines and breast cancer cell lines. β-Actin was used as a control to confirm equal loading of protein. Figure S2. Subject inclusion and study profile. Figure S3. Serum CPT1A levels in different pathologic types of breast cancer. Serum CPT1A levels of breast cancer patients with cancer in situ, invasive ductal carcinoma, invasive lobular carcinoma, invasive papillary carcinoma, mucinous carcinoma and other types, in the training set (left) and test set (right), respectively. Statistical significance was determined by the Mann–Whitney U test. **p

Objectives: The post-imaging, mathematical predictive model was established by combining demographic and imaging characteristics with a pulmonary nodule risk score. The prediction model provides directions for the treatment of pulmonary nodules. Many studies have established predictive models for pulmonary nodules in different populations. However, the predictive factors contained in each model were significantly different. We hypothesized that applying different models to local research groups will make a difference in predicting the benign and malignant lung nodules, distinguishing between early and late lung cancers, and between adenocarcinoma and squamous cell carcinoma. In the present study, we compared four widely used and well-known mathematical prediction models. Materials and methods: We performed a retrospective study of 496 patients from January 2017 to October 2019, they were diagnosed with nodules by pathological. We evaluate models’ performance by viewing 425 malignant and 71 benign patients’ computed tomography results. At the same time, we use the calibration curve and the area under the receiver operating characteristic curve whose abbreviation is AUC to assess one model’s predictive performance. Results: We find that in distinguishing the Benign and the Malignancy, Peking University People’s Hospital model possessed excellent performance (AUC = 0.63), as well as differentiating between early and late lung cancers (AUC = 0.67) and identifying lung adenocarcinoma (AUC = 0.61). While in the identification of lung squamous cell carcinoma, the Veterans Affairs model performed the best (AUC = 0.69). Conclusions: Geographic disparities are an extremely important influence factors, and which clinical features contained in the mathematical prediction model are the key to affect the precision and accuracy.

Recently, the outbreak of a serious infectious disease of unknown etiology was noted in Percocypris pingi (Tchang, 1930) farms in Yunnan province. Due to currently limited information, we aimed to identify the pathogen isolates, determine the susceptibility of the isolates, evaluate the pathogenicity and analyze the genome of the representative strain. Ten strains of Gram-negative rods were isolated from diseased P. pingi and the isolates were identified as Plesiomonas shigelloides based on biochemical characteristics, 16S rRNA gene sequencing and species-specific PCR detection. The results of susceptibility analysis showed that two selected strains LS1 and LL2 were resistant to ampicillin, penicillin G, trimethoprim/sulfamethoxazole, tetracycline, enrofloxacin, nalidixic acid and enoxacin. A virulence assay indicated that the pathogen was virulent to zebrafish. Genomic analysis revealed that the LS1 isolate was closely related to strain GN7, which was isolated from animal farms. To the best of our knowledge, this is the first report of P. shigelloides as a pathogen of P. pingi. This study will provide a rational framework for exploration of epidemiological analysis of P. shigelloides in fish diseases and would further benefit conservation of the species.

The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.

Figure S1. The expression level and survival analysis of miR-21 in breast cancer patients from TCGA database. A. The overall survival rates of breast cancer patients (n = 1061) with low or high expression levels of miR-21 were estimated with the Kaplan–Meier method by log-rank test according to data from the Cancer Genome Atlas (TCGA) on Kaplan–Meier Plotter platform (http://kmplot.com/analysis/). B. The relative miR-21 expression levels in normal breast tissue (n = 61) and invasive breast cancer tissue (n = 76) were analyzed according to data from TCGA provided by Oncomine (https://www.oncomine.org). (PDF 189 kb)

Metastasis is the leading cause of high mortality in lung cancer patients, and metastatic lung cancer is difficult to treat. miRNAs are involved in various biological processes of cancer, including metastasis. Our previous studies revealed that miR-25 promoted non-small-cell lung cancer (NSCLC) cell proliferation and suppressed cell apoptosis by directly targeting TP53 and MOAP1. In this work, we further explored the miR-25 expression in NSCLC patients in the Cancer Genome Atlas (TCGA) database and measured the miR-25 expression levels in the tissues of NSCLC patients and cell lines. miR-25 was overexpressed in both NSCLC tissues and cell lines. NSCLC patients who expressed a higher level of miR-25 exhibited worse overall survival than those with a lower level of miR-25. Overexpression of miR-25 enhanced NSCLC cell migration and invasion, while the inhibition of miR-25 exhibited the opposite effects. We identified the large tumor suppressor homology 2 (LATS2) as a new target gene of miR-25 in lung cancer. The effects of miR-25 on promoting NSCLC cell migration and invasion were at least partially due to activation of the Hippo signaling pathway. Additionally, miR-25 antagomir inhibited xenograft tumor growth and metastasis by the upregulation of LATS2. Taken together, our findings demonstrate that miR-25 contribute to lung cancer cell proliferation and metastasis by targeting the LATS2/YAP signaling pathway, which implicate miR-25 as a promising therapeutic target for lung cancer metastasis. Given that oxidative stress induces the overexpression of miR-25 and plays a critical role in cancer progression, this study establishes miR-25 as an intermediate between oxidative stress and lung cancer metastasis.

Background Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. Methods qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan–Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial–mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. Results Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. Conclusions These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21–LZTFL1–EMT axis might be a promising strategy in breast cancer therapy. Trial registration Retrospectively registered. Electronic supplementary material The online version of this article (10.1186/s12885-019-5951-3) contains supplementary material, which is available to authorized users.

Background Studies of the association between the interleukin-1β gene (IL-1β) (+ 3953C/T, − 511T/C) and interleukin-6 gene (IL-6) (− 174G/C) polymorphisms and susceptibility to tuberculosis (TB) have yielded inconsistent results. The aim of this study was to investigate the relationship between these polymorphisms and TB risk by this meta-analysis. Methods We systematically searched published literatures on IL-1β gene and IL-6 gene polymorphisms and tuberculosis risk by the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library databases, and identified outcome data from all articles. Statistical analysis was performed using Stata 12.0. A total of 15 studies comprising 3983TB patients and 3996 controls were included in the present study. Results We found that the IL-6 − 174C/G polymorphism might be associated with decreased risk of TB (C vs. G: OR = 0.77, 95% CI = 0.64–0.91; CG vs. GG: OR = 0.72, 95% CI = 0.57–0.90; CC + CG vs. GG: OR = 0.71, 95% CI = 0.57–0.88). In the stratified analysis by ethnicity, significantly decreased risk were observed for IL-1β − 511T/C polymorphism in Africans (C allele vs. T allele: OR = 0.86, 95% CI = 0.74–0.99; CC vs. TT: OR = 0.74, 95% CI = 0.55–0.99). Moreover, the IL-6 − 174 C/G polymorphism was also associated with decreased risk of TB in Asians (C vs. G: OR = 0.71, 95% CI = 0.54–0.93; CG vs. GG: OR = 0.61, 95% CI = 0.44–0.85; CC + CG vs. GG: OR = 0.63, 95% CI = 0.46–0.86). We also performed the analyses by sample types in IL-6 − 174 C/G polymorphism, and significant decreased TB risk was observed in pulmonary tuberculosis group (C allele vs. G allele: OR = 0.69, 95% CI = 0.52–0.93; CG vs. GG: OR = 0.69, 95% CI = 0.52–0.91; CC + CG vs. GG: OR = 0.71, 95% CI = 0.55–0.93), and pulmonary tuberculosis plus extra-pulmonary tuberculosis mixed group (CC vs. GG: OR = 0.44, 95% CI = 0.22–0.88; CC vs. CG + GG: OR = 0.48, 95% CI = 0.25–0.94). Conclusions This meta-analysis indicates that the IL-1β − 511T/C polymorphism is associated with TB decreased risk in Africans, and IL-6 − 174C/G polymorphism in Asians. Further well-designed, large scale studies are required to confirm this conclusion.

To determine the role of miR-25 in non-small cell lung cancer (NSCLC), we first detected miR-25 expression in clinical specimens and lung cancer cell lines by quantitative real-time polymerase chain reaction. The levels of miR-25 were elevated in the plasma of NSCLC patients and NSCLC cell lines. Transfection of A549 and 95-D cells with a miR-25 inhibitor resulted in reduced cell proliferation and enhanced apoptosis. Moreover, the modulator of apoptosis 1 (MOAP1) gene was identified as a novel target of miR-25. The ability of miR-25 to promote cell proliferation and block apoptosis is attributable to its effect on MOAP1 suppression. In addition, miR-25 antagomir significantly inhibited lung cancer growth via upregulation of MOAP1 in a mouse xenograft model. Collectively, these data demonstrate that miR-25 is an important biomarker for lung cancer, and miR-25 promotes cell proliferation and inhibits apoptosis in NSCLC cells by negatively regulating MOAP1 expression.

Pancreatic cancer (PC) is a highly invasive tumor with early metastasis and poor prognosis, yet the mechanisms for tumor progression have not been fully elucidated. Emerging evidence indicates that microRNA-331-3p (miR-331-3p) plays an important role in the progression of diverse human cancers. Here, we found that miR-331-3p was significantly upregulated in tumor specimens of PC patients and PC cell lines. Functional studies showed that downregulation of miR-331-3p inhibited PC cell proliferation and epithelial-mesenchymal transition (EMT)-mediated metastasis in vitro. Furthermore, suppression of tumorigenicity 7 like (ST7L) was identified as a novel target gene of miR-331-3p. Tumor promotion effects of miR-331-3p were partially reversed by ST7L re-expression. In addition, miR-331-3p antagomir suppressed PC tumor growth and metastasis via upregulation of ST7L in xenograft mice. In summary, these results demonstrate that miR-331-3p is a tumor-promoting microRNA (miRNA) in PC cells and a promising biomarker for PC.

Atherosclerosis (AS) is chronic inflammation in response to lipid accumulation. MicroRNA-155 (miR-155) is being increasingly studied to evaluate its potential as diagnostic biomarkers and therapeutic targets in many diseases. However, delineating the role of miR-155 in AS remains difficult. Here, we detected constitutive expression of several microRNAs (miRNAs) possibly associated with cardiovascular disease in foam cells and clinical specimens from patients with AS. Among them, we found that the level of miR-155 in foam cells was the most significantly elevated in a dose- and time-dependent manner. In addition, the expression of miR-155 was elevated in the plasma and plaque of patients with AS. We also reported for the first time that miR-155 targets calcium-regulated heat stable protein 1 (CARHSP1), which regulates the stability of tumor necrosis factor alpha (TNF-α) mRNA. Furthermore, we investigated the mechanism by which the miR-155 level is elevated. miR-155 upregulation is due to transcriptional regulation by nuclear factor (NF)-κB, which is activated by the inflammatory factor TNF-α. In summary, increased miR-155 relieves chronic inflammation by a negative feedback loop and plays a protective role during atherosclerosis-associated foam cell formation by signaling through the miR-155–CARHSP1–TNF-α pathway.

Breast cancer, one of the most common diseases among women, is regarded as a heterogeneous and complicated disease that remains a major public health concern. Recently, owing to the development of next-generation sequencing technologies, long non-coding RNAs have received extensive attention. Numerous studies reveal that long non-coding RNAs are playing important roles in tumor development. Although the biological function and molecular mechanisms of long non-coding RNAs remain enigmatic, recent researchers have demonstrated that an array of long non-coding RNAs express abnormally in cancers, including breast cancer. Herein, we summarized the latest literature about long non-coding RNAs in breast cancer, with a particular focus on the multiple molecular roles of regulatory long non-coding RNAs that regulate cell proliferation, invasion, metastasis, and apoptosis.

The Genotype MTBDRsl is a new-generation PCR-based line-probe assay for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. The aim of this meta-analysis was to evaluate the performance of Genotype MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol in comparison with the phenotypic drug susceptibility test.We searched Pubmed, Embase and the Cochrane Library and calculated the sensitivity, the specificity, the positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), corresponding 95% confidence interval (CI), and the area under the summary receiver operating characteristic (SROC) curves (AUC), and tested heterogeneity in accuracy estimates with the Spearman correlation coefficient and Chi-square.The summarized sensitivity (95% CI), specificity (95% CI), and AUC (standard error) were 0.869 (0.847-0.890), 0.973 (0.965-0.979) and 0.9690 (0.0188) for fluoroquinolones, 0.868 (0.829-0.900), 0.998 (0.994-0.999) and 0.9944 (0.0050) for amikacin, 0.879 (0.838-0.914), 0.970 (0.958-0.978) and 0.9791 (0.0120) for capreomycin, 0.501 (0.461-0.541), 0.991 (0.983-0.996) and 0.9814 (0.0114) for kanamycin and 0.686 (0.663-0.709), 0.871 (0.852-0.888) and 0.7349 (0.0639) for ethambutol, respectively.The genotype MTBDRsl demonstrate excellent accuracy for detecting drug resistance to fluoroquinolones, amikacin, and capreomycin, but it may not be an appropriate choice for detection of kanamycin and ethambutol.

Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well-understood, and the prognosis for patients with HCC remains very poor. To disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method. In this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy. The study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients.

Background Primary hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. However, the molecular pathogenesis of HCC is not well-understood, and the prognosis for patients with HCC remains very poor. Methods To disclose detailed genetic mechanisms in hepatocellular carcinoma (HCC) with a view toward development of novel therapeutic targets, we analyzed expression profiles HCCs and their corresponding noncancerous tissues by using bioinformatics method. Results In this paper, we report the identification of genes whose expression has been altered and the changed bio-pathways during hepatocarcinogenesis. Hepatoma cells infect intracellular and intercellular signal transduction through Focal adhesion and cause abnormal expression of important intracellular signaling pathway. In addition, it is worth mentioning that some small molecules still restored to the state similar to normal cells, such as bambuterol and lovastatin. This member gene set would serve as a pool of lead gene targets for the identification and development of novel diagnostic and therapeutic biomarkers to greatly improve the clinical management of HCC patients with different risks of recurrence after curative partial hepatectomy. Conclusions The study has great significance for gene therapy and pharmacotherapy and provides a new treatment entry point and a potential new clinical drug for HCC patients.

Various studies have reported that Huaier possesses anti-tumor effects. However, the mechanisms are not completely elucidated. Here, we found 66 differentially expressed miRNAs in Huaier-treated pulmonary adenocarcinoma A549 cells, with upregulation of miR-26b-5p. Transfection of A549 cells with miR-26b-5p mimic inhibited proliferation and induced apoptosis, while transfection of Huaier-treated A549 cells with a miR-26b-5p inhibitor reversed the effects of Huaier. EZH2 was verified as the target of miR-26b-5p. Thus, our findings indicate that Huaier might suppress proliferation and induce apoptosis in lung cancer cells via a miR-26b-5p-EZH2-mediated approach, which provides a new perspective for understanding the anti-tumor effects of Huaier.