Patients with hematogenous metastatic lung cancer displayed significantly increased platelet count and aggregation compared to lung cancer patients without hematogenous metastasis. The mechanism underlying the correlation between the lung cancer hematogenous metastasis and platelet activation remains unknown. In the present study, we explored the role of microRNA-223 (miR-223) derived from platelets in modulating lung cancer cell invasion. Our results demonstrated that platelets from NSCLC patients contain higher level of miR-223 than that from healthy subjects. The concentration of miR-223 in the platelet-secreted microvesicles (P-MVs) from NSCLC patients was also increased compared to that from healthy subjects. Incubation of human lung cancer A549 cells with P-MVs resulted in rapid delivery of miR-223 into A549 cells, in which platelet miR-223 targeted EPB41L3 and thus promoted A549 cell invasion. The effect of P-MVs on reducing EPB41L3 in A549 cells but promoting tumor cell invasion could be largely abolished by depletion of miR-223 via transfection with miR-223 antagomir. The role of EPB41L3 in inhibiting A549 cell invasion was further validated by directly downregulating EPB41L3 via transfecting cells with EPB41L3 siRNA or miR-223 mimic. Our study demonstrates for the first time that platelet-secreted miR-223 via P-MVs can promote lung cancer cell invasion via targeting tumor suppressor EPB41L3.

ERBB3, one of the four members of the ErbB family of receptor tyrosine kinases, plays an important role in breast cancer etiology and progression. In the present study, we aimed to identify novel miRNAs that can potentially target ERBB3 and their biological functions. The expression levels of miR-143/145 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. We used bioinformatic analyses to search for miRNAs that can potentially target ERBB3. Luciferase reporter plasmids were constructed to confirm direct targeting. Furthermore, the biological consequences of the targeting of ERBB3 by miR-143/145 were examined by cell proliferation and invasion assays in vitro and by the mouse xenograft tumor model in vivo. We identified an inverse correlation between miR-143/145 levels and ERBB3 protein levels, but not between miR-143/145 levels and ERBB3 mRNA levels, in breast cancer tissue samples. We identified specific targeting sites for miR-143 and miR-145 (miR-143/145) in the 3’-untranslated region (3’-UTR) of the ERBB3 gene and regulate ERBB3 expression. We demonstrated that the repression of ERBB3 by miR-143/145 suppressed the proliferation and invasion of breast cancer cells, and that miR-143/145 showed an anti-tumor effect by negatively regulating ERBB3 in the xenograft mouse model. Interestingly, miR-143 and miR-145 showed a cooperative repression of ERBB3 expression and cell proliferation and invasion in breast cancer cells, such that the effects of the two miRNAs were greater than with either miR-143 or miR-145 alone. Taken together, our findings provide the first clues regarding the role of the miR-143/145 cluster as a tumor suppressor in breast cancer through the inhibition of ERBB3 translation. These results also support the idea that different miRNAs in a cluster can synergistically repress a given target mRNA.

Background: In eukaryotes, miR-16 is an important microRNA (miRNA) that is involved in numerous biological processes. However, it is not fully understood how miR-16 executes its physiological functions. In the present study, we aimed to identify novel miR-16 targets and study their biological functions. Methods: Candidate target genes of miR-16 were screened by microarray analysis of mRNA levels in several cancer cell lines with enhanced miR-16. Three bioinformatics algorithms, including TargetScan, PicTar, and miRanda, were used in combination to calculate the miR-16 targets. The expression levels of miR-16 and target mRNA were examined by relative quantification RT-PCR, and the expression levels of target protein were detected by Western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. The effect of miR-16 and target gene on cell viability was evaluated using MTT assays. The effects of miR-16 and target gene on apoptosis and cell cycle distribution were evaluated by flow cytometry analysis. Results: By overexpressing miR-16 in several cancer cell lines and measuring global mRNA levels using microarray analysis, we identified 27 genes that may be regulated by miR-16. After the bioinformatics filtering process, 18 genes were selected as candidate miR-16 targets. Furthermore, we experimentally validated three of these candidates, MAP7 (microtubule-associated protein 7), PRDM4 (PR domain containing 4) and CDS2 (CDP-diacylglycerol synthase 2), as direct targets of miR-16. Finally, we demonstrated that miR-16 targeting MAP7 played a critical role in regulating proliferation but not apoptosis and cell cycle progression in cancer cells. Conclusion: In summary, the present study identifies several novel miR-16 targets and illustrates a novel function of miR-16 targeting MAP7 in modulating proliferation in cancer cells.

Tuberculosis (TB), one of the ancient and deadliest diseases, is a chronic immune disorder caused by Mycobacterium tuberculosis (Mtb) infection. Due to the lack of ideal diagnostic and therapeutic markers, TB is still posing a major health, social, and economic burden worldwide. Circular RNA (circRNA), a newly discovered endogenous RNA, is abundant and stable in the cytoplasm and has tissue specificity. More and more studies suggested circRNA is involved in a variety of human pathological and physiological processes. Recently, several studies have confirmed circRNAs not only existed in the serum but also could serve as ideal biomarkers for detecting diseases since the circRNAs have continuous, stable, and covalently closed circular structures and are not easily degraded by nucleases. In this study, we screened the circRNA expression profiles in active TB serum samples and healthy volunteers serum samples by circRNA microarrays. Then, we performed qRT-PCR to verified the dysregulated circRNAs and ROC curve analysis to evaluate the value of circRNAs for TB diagnosis. The results showed circRNA_051239, circRNA_029965, and circRNA_404022 could serve as biomarkers for TB diagnosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with low survival time. Since the pathophysiological progression of IPF is closely associated with immunological and inflammatory responses, immune biomarkers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-high density lipoprotein ratio (MHR), have the potential to predict overall survival in IPF patients.Methods: A total of 278 patients with IPF were finally enrolled. The demographic and clinical characteristics of the patients at baseline were recorded. Multivariable Cox regression analysis was used to evaluate the association between the three biomarkers and overall survival in both the total cohort and acute exacerbation subgroup.Results: The median follow-up was 5.84 months. After adjusting for confounders, we found that only elevated NLR was associated with worse overall survival (OR = 1.019, 95% CI 1.001-1.037, P =0.041) by using multivariable Cox regression analysis. In 116 acute exacerbation IPF patients, the results of the Cox multiple regression model also indicated that the NLR was a significant prognostic factor (OR= 1.022, 95% CI 1.001-1.044, P =0.036). The NLR before death was also significantly higher than that at admission in nonsurvival acute exacerbation IPF patients (P=0.014). No significant differences were found in PLR (P=0.739) or MHR changes (P=0.478).Conclusions: Our results indicated that elevated NLR expression is associated with shorter overall survival in IPF patients, which is independent of other prognostic factors. The NLR may be regarded as a reliable prognostic biomarker for IPF patients.

Objective: Vitamin D deficiency was associated with CTD-ILD and reduced lung function. We sought to confirm that lower Vitamin D level would be related to shorter survival times. Results: The CTD-ILD patients had lower Vitamin D level (P<0.05). Among patients with CTD-ILD who have improved lung function after treatment, elevation of Vitamin D level was positively associated with Delta FVC (%),Delta FEV1(%) and Delta DLCO-SB (%). The median survival time of patients with high serum 25(OH)D level was significantly longer than the patients with low 25(OH)D level group (16.5 months vs14.0 months, P=0.007). The Vitamin D was identified as an independent prognostic factor with a hazard ratio of 0.869 (95% CI 0.772-0.977, P=0.019). Conclusions: Vitamin D level was lower in patients with CTD-ILD and associated with poor prognosis. Continuous levels of Vitamin D may be an important serum biomarker of prognosis. Methods: 85 CTD-ILD patients, 71 Idiopathic pulmonary fibrosis (IPF) patients and 78 healthy control patients were included in the study. In the subgroup analysis, the CTD-ILD patients were divided into anti-MDA5 antibody-positive group and anti-MDA5 antibody-negative group according to the serum autoantibodies results. The survival analysis evaluated effect of Vitamin D level on disease prognosis.