Circular RNA and its mechanisms in disease: From the bench to the clinic.

Triple-negative (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. Chemotherapy remains the standard of care for TNBC treatment, but unfortunately, patients frequently develop resistance. Accordingly, in recent years, tremendous effort has been made into elucidating the mechanisms of TNBC chemoresistance with the goal of identifying new molecular targets. It has become evident that the development of TNBC chemoresistance is multifaceted and based on the elaborate interplay of the tumor microenvironment, drug efflux, cancer stem cells, and bulk tumor cells. Alterations of multiple signaling pathways govern these interactions. Moreover, TNBC’s high heterogeneity, highlighted in the existence of several molecular signatures, presents a significant obstacle to successful treatment. In the present, in-depth review, we explore the contribution of key mechanisms to TNBC chemoresistance as well as emerging strategies to overcome them. We discuss novel anti-tumor agents that target the components of these mechanisms and pay special attention to their current clinical development while emphasizing the challenges still ahead of successful TNBC management. The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment and highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies.

https://www.mdpi.com/2073-4409/8/9/957/pdf

Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer-How We Can Rise to the Challenge.

circRNAs in Cancer

CircRNAs and cancer: Biomarkers and master regulators.

Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

/pdf/noncoding-rnas-in-gastric-cancer-implications-for-drug-3w5e7wjv27.pdf

Noncoding RNAs in gastric cancer: implications for drug resistance

// Lingshuang Lu 1, * , Jian Sun 2, * , Peiyi Shi 1 , Weimin Kong 2 , Kun Xu 3 , Biyu He 3 , Simin Zhang 1, 3 and Jianming Wang 1 1 Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China 2 Department of Thoracic Surgery, The First People′s Hospital of Yancheng City, Yancheng, 224001, China 3 Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China * These authors have contributed equally to this work Correspondence to: Jianming Wang, email: jmwang@njmu.edu.cn Keywords: breast cancer, RNA, noncoding RNA, circRNA, biomarker Received: December 14, 2016      Accepted: April 03, 2017      Published: April 21, 2017 ABSTRACT Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.

Identification of circular RNAs as a promising new class of diagnostic biomarkers for human breast cancer.

MicroRNAs in the prognosis of triple-negative breast cancer: A systematic review and meta-analysis.

A variety of abnormalities in vitamin D metabolism have been reported in patients with active tuberculosis. However, intervention trials have produced inconsistent results. We hypothesized that genetic and epigenetic changes in the key genes of the vitamin D metabolic pathway may partly explain the differences between studies. We performed a case-control study followed by a prospective cohort study. We recruited 122 patients with pulmonary tuberculosis and 118 healthy controls. The serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were measured. The methylation of the promoter regions of key genes in the vitamin D metabolic pathway (CYP24A1, CYP27A1, CYP27B1, CYP2R1, and VDR) was detected using the Illumina MiSeq platform. The specific methylation profiles were examined as epigenetic biomarkers. The sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to estimate the predictive value of the biomarkers. The baseline serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations in the cases were significantly lower than those in the controls (51.60 ± 27.25 nmol/L vs. 117.50 ± 75.50 nmol/L, Z = − 8.515, P < 0.001; 82.63 ± 51.43 pmol/L vs. 94.02 ± 49.26 pmol/L, Z = − 2.165, P = 0.03). We sequenced 310 CpG sites in five candidate genes. After Bonferroni correction, there were 55 differentially methylated CpG sites between cases and controls; 41.5% were in the CYP27B1 gene, 31.7% were in the CYP24A1 gene, 14.7% were in the VDR gene, and 12.3% were in the CYP27A1 gene. When we designated the CpG sites that remained significant after the Bonferroni correction as the biomarkers, the area under the curve (AUC) for the cumulative methylation was 0.810 (95% CI 0.754–0.866). There was an interaction between CYP27A1 methylation level and 1,25-dihydroxyvitamin D concentration associated with the risk of TB (ORinteraction = 4.11, 95% CI 1.26–13.36, P = 0.019). The serum 1,25-dihydroxyvitamin D concentration at the end of the intensive treatment stage was related to a patient’s prognosis (P = 0.008). There were 23 CpG sites that were individually related to the treatment outcomes, but the relationships were not significant after the Bonferroni correction. Both serum vitamin D concentrations and the methylation levels of key genes in the vitamin D metabolic pathway are related to the risk and prognosis of tuberculosis.

/pdf/vitamin-d-and-the-promoter-methylation-of-its-metabolic-8puf8jh014.pdf

Vitamin D and the promoter methylation of its metabolic pathway genes in association with the risk and prognosis of tuberculosis

Background Tuberculosis (TB) infection interferes with the health-related quality of life (HRQOL), including physical, social, mental, emotional and financial domains of individuals. The goal of this scoping review is to outline the most frequent mental issues encountered by TB patients and evaluate the effects of mental health on TB treatment outcomes. Our findings identify research gaps that could help bridge the overall treatment outcomes in the near future. Method A systematic stepwise approach was adopted to search online resource databases like PubMed, Web of science, and gray literature to retrieve published scientific articles for the review. Titles and abstracts of selected studies were examined for their possible eligibility. The studies matching our eligibility criteria were taken into account for this scoping review. Results One hundred and ninety three articles were retrieved out of which 26 met the final inclusion criteria. We found that studies adopting interventional approaches reported good mental wellbeing outcomes and better medical compliance as compared with studies that just investigated the subjects. The data represented 15 countries including three low-income countries (LICs), four low-middle-income-countries (LMICs), seven upper-middle-income countries (UMICs), and one high-income country (HIC). Conclusion Depression, anxiety, and poor social support, and stigma affect the wellbeing of individuals across the globe irrespective of age, race, demographic characteristics, geographical location, and social status.

Mental Health Status and Its Impact on TB Treatment and Its Outcomes: A Scoping Literature Review

Introduction Circular RNAs (circRNAs) function as efficient microRNA sponges with gene-regulatory potential and are promising cancer biomarkers. In this study, we used the Arraystar Human circRNA Array to construct a genome-wide circRNA profile of esophageal squamous cell cancer (ESCC) and breast cancer (BC). Patients and methods Expression levels between cancer lesions and adjacent normal-appearing tissues were compared. We observed 469 upregulated circRNAs and 275 downregulated circRNAs in ESCC. Hsa_circRNA_103670 was upregulated 20.3-fold, while hsa_circRNA_030162 was downregulated 12.1-fold. For BC, 715 circRNAs were upregulated, and 440 circRNAs were downregulated. Hsa_circRNA_005230 was upregulated 12.2-fold, while hsa_circRNA_406225 was downregulated 12.4-fold. Results When we set the criteria as fold change in expression ≥2 between cancer and adjacent normal-appearing tissue with a P-value <0.01, there were 22 common circRNAs (11 upregulated and 11 downregulated) in relation to both ESCC and BC. Gene ontology and the Kyoto encyclopedia of genes and genomes analyses showed that these circRNAs were involved in the tumorigenesis of human cancers. Conclusion Our study revealed that circRNAs are promising candidates as valuable biomarkers for ESCC and BC, although relevant research is still in its infancy and the functional role of specific circRNAs in tumorigenesis is just starting to be elucidated.

/pdf/profiles-of-differentially-expressed-circrnas-in-esophageal-3lpus5arnd.pdf

Profiles of differentially expressed circRNAs in esophageal and breast cancer.

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