The Current View on the Helicase Activity of RNA Helicase A and Its Role in Gene Expression.

RNA helicase A (RHA) is a DExH-box helicase that plays regulatory roles in a variety of cellular processes, including transcription, translation, RNA splicing, editing, transport, and processing, microRNA genesis and maintenance of genomic stability. It is involved in virus replication, oncogenesis, and innate immune response. RHA can unwind nucleic acid duplex by nucleoside triphosphate hydrolysis. The insight into the molecular mechanism of helicase activity is fundamental to understanding the role of RHA in the cell. Herein, we reviewed the current advances on the helicase activity of RHA and its relevance to gene expression, particularly, to the genesis of circular RNA.

Effects of inflammatory and anti-inflammatory environments on the macrophage mitochondrial function.

Mitochondrial response to inflammation is crucial in the metabolic adaptation to infection. This study aimed to explore the mitochondrial response under inflammatory and anti-inflammatory environments, with a focus on the tricarboxylic acid (TCA) cycle. Expression levels of key TCA cycle enzymes and the autophagy-related protein light chain 3b (LC3b) were determined in raw 264.7 cells treated with lipopolysaccharide (LPS) and metformin (Met). Additionally, reactive oxygen species (ROS) levels and mitochondrial membrane potential were assessed using flow cytometry. Moreover, 8-week-old C57BL/6J mice were intraperitoneally injected with LPS and Met to assess the mitochondrial response in vivo. Upon LPS stimulation, the expression of key TCA enzymes, including citrate synthase, α-ketoglutarate dehydrogenase, and isocitrate dehydrogenase 2, and the mitochondrial membrane potential decreased, whereas the levels of LC3b and ROS increased. However, treatment with Met inhibited the reduction of LPS-induced enzyme levels as well as the elevation of LC3b and ROS levels. In conclusion, the mitochondrial TCA cycle is affected by the inflammatory environment, and the LPS-induced effects can be reversed by Met treatment.

Correction to: EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis.

An amendment to this paper has been published and can be accessed via the original article.

Study on the Expression Levels and Clinical Significance of PD-1 and PD-L1 in Plasma of NSCLC Patients.

As new members of the CD28/B7 costimulatory superfamily, PD-1 (programmed cell death 1) and its ligand PD-L1 (programmed cell death ligand 1) mediate a negative costimulatory signal, which inhibits functioning and proliferation of T and B cells, and reduce interleukin-2, interleukin-10, and interferon-γ secretion. This inhibitory pathway plays an important role in immune escape and the microenvironment of the tumor, and closely related to tumor progression. sPD-1 and sPD-L1 are the soluble form of PD-1 and PD-L1 in peripheral blood, which had not been well investigated. In this study, sPD-1 and sPD-L1 level in peripheral blood of non-small cell lung cancer (NSCLC) patients were determined, and their correlation to clinicopathologic features and long-term survival of these patients were analyzed, so as to provide references for further investigations. Plasma sPD-1 and sPD-L1 levels in 88 NSCLC patients and 40 healthy controls were determined by enzyme-linked immunosorbent assay, and their correlation to clinicopathologic features and long-term survival of these patients were analyzed. Our study showed that the plasma sPD-1 and sPD-L1 were higher in NSCLC patients than in healthy controls, and plasma sPD-L1 and sPD-L1/sPD-1 ratio independently and positively correlated with overall survival of NSCLC patients. This study provides a reference for the assessment of prognosis and risk stratification for NSCLC patients, as well as for immune treatment of cancer.

EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis.

BACKGROUND: Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). METHODS: A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. RESULTS: In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. CONCLUSIONS: Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM.

Clinical Benefits of Acupuncture for the Reduction of Hormone Therapy-Related Side Effects in Breast Cancer Patients: A Systematic Review.

IMPORTANCE: Acupuncture can help reduce unpleasant side effects associated with endocrine therapy for breast cancer. Nevertheless, comprehensive evaluation of current evidence from randomized controlled trials(RCTs) is lacking. OBJECTIVE: To estimate the efficacy of acupuncture for the reduction of hormone therapy-related side effects in breast cancer patients. EVIDENCE REVIEW: RCTs of acupuncture in breast cancer patients that examined reductions in hormone therapy-related side effects were retrieved from PubMed, EMBASE, Web of Science, Ovid MEDLINE, and Cochrane Library databases through April 2016. The quality of the included studies was evaluated according to the 5.2 Cochrane Handbook standards, and CONSORT and STRICTA (Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture) statements. INTERVENTION: Interventions included conventional acupuncture treatment compared with no treatment, placebo, or conventional pharmaceutical medication. Major outcome measures were the alleviation of frequency and symptoms and the presence of hormone therapy-related side effects. Findings/Results. A total of 17 RCTs, including a total of 810 breast cancer patients were examined. The methodological quality of the trials was relatively rigorous in terms of randomization, blinding, and sources of bias. Compared with control therapies, the pooled results suggested that acupuncture had moderate effects in improving stiffness. No significant differences were observed in hot flashes, fatigue, pain, gastrointestinal symptoms, Kupperman index, general well-being, physical well-being, tumor necrosis factor (TNF), and interleukin (IL). CONCLUSIONS: Acupuncture therapy appears to be potentially useful in relieving functional stiffness. However, further large-sample trials with evidence-based design are still needed to confirm these findings.

CircNT5E Acts as a Sponge of miR-422a to Promote Glioblastoma Tumorigenesis.

Circular RNA and long noncoding RNA function as efficient miRNA sponges that regulate gene expression in eukaryotes. However, the sponges of functional miRNAs in glioblastoma remain largely unknown. Here, we identify a subset of circRNAs and lncRNAs that are specifically increased in miR-422a-downregulated glioblastoma tissues. We characterized a novel circRNA derived from NT5E, named circNT5E, that is regulated by ADARB2 binding to sites flanking circRNA-forming introns. We hypothesized that circNT5E may serve as a sponge against miR-422a in glioblastoma tumorigenesis. circNT5E controlled multiple pathologic processes, including cell proliferation, migration, and invasion. circNT5E directly bound miR-422a and inhibited miR-422a activity. Furthermore, circNT5E was observed to sponge other miRNAs, exhibiting tumor suppressor-like features in glioblastoma. Taken together, these findings highlight a novel oncogenic function of circRNA in glioblastoma tumorigenesis.Significance: Microarray profiling of circRNA/lncRNA/mRNA in glioblastoma identifies circNT5E as an oncogenic circular RNA and a sponge of miR-422a. Cancer Res; 78(17); 4812-25. ©2018 AACR.

Reporting Characteristics and Quality of Systematic Reviews of Acupuncture Analgesia.

BACKGROUND: Evaluating the clinical efficacy of acupuncture analgesia with systematic reviews (SRs) has attracted wide interest. OBJECTIVE: To collect a sample of published SRs on acupuncture analgesia in PubMed and examine them in terms of reporting characteristics and quality. METHODS: A search in PubMed was performed in January 2016. All SRs on acupuncture analgesia were included. To assess the quality of the SRs, AMSTAR tool and PRISMA Statements were used. RESULTS: One hundred and nine SRs were included in our analysis, the yearly number of publications ranging from 1 in 1997 to 15 in 2015. Only 17% of these publications were Cochrane Systematic Reviews, and 94% were published in Science Citation Index journals. The United Kingdom was the country with the higher number of publications. Low back pain, headache, cancer pain, and labor pain were the most reported diseases or phenotypes. Nearly 73% of these SRs conducted a meta-analysis, 58% revealed positive results, 53% used RevMan software to analyze data, and 44% used the Cochrane Risk of Bias Tool for quality assessment. Only a few SRs assessed the likelihood of publication bias, reported details about the protocol and the registration information, and performed additional analyses. CONCLUSIONS: The quantity and the quality of SRs regarding acupuncture analgesia have been promoted in recent years. More effort should be expended on the assessment of publication bias, the provision of detailed information about the protocol and the registration process, and the implementation of additional analyses to improve the validity of the SRs.

Could yoga practice improve treatment-related side effects and quality of life for women with breast cancer? A systematic review and meta-analysis.

AIM: To determine if yoga as a complementary and alternative therapy was associated with enhanced health and treatment-related side effects in patients with breast cancer. This systematic review examines whether yoga practice provides any measurable benefit, both physically and psychologically, for women with breast cancer. METHODS: PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) throughout June 2013. We evaluated the quality of the included studies by the Cochrane Handbook 5.2 standards and analyzed the data using the Stata software, version 10.0. Meta-regression and subgroup analysis were also performed to identify additional predictors of outcome and to assess heterogeneity. RESULTS: Sixteen RCTs with a total of 930 participants were included. Comparing yoga groups to control groups, there was a statistically significant difference in overall health-related quality of life, depression, anxiety and gastrointestinal symptoms. Meta-regression analyses revealed that the duration of yoga practice and type of control group partly explained the heterogeneity. Subgroup analyses revealed that yoga had a positive effect on anxiety only when it had been practiced for longer than 3 months. Only the wait-list control group showed an effect of yoga on physical well-being. CONCLUSION: The current evidence demonstrates that yoga practice could be effective in enhancing health and managing some treatment-related side effects for patients recovering from breast cancer. In future clinical studies, clinicians should consider the patient's wishes along with the current best evidence of the effects of yoga practice in their clinical decision-making.

Does pelvic floor muscle training augment the effect of surgery in women with pelvic organ prolapse? A systematic review of randomized controlled trials.

BACKGROUND: Pelvic floor muscle training (PFMT) is often used as a treatment for pelvic organ prolapse (POP) and can improve function. However, the effectiveness of this modality as an adjunct to prolapse surgery for women with POP is unknown. AIMS: To evaluate whether the use of pelvic floor muscle training as an adjunct to prolapse surgery is superior to surgery alone for women with pelvic organ prolapse. METHODS: We searched PubMed, Embase, the Cochrane Library, and the Web of Science from their inception dates to June 30, 2014 for data describing randomized controlled trials (RCTs) that compare the efficacy of PFMT with or without lifestyle modification plus surgery versus surgery alone for women with POP. Additional relevant studies were identified by searching the references of retrieved articles and using Google Scholar. Two investigators independently reviewed and selected relevant studies that met the pre-specified inclusion criteria, extracted the data, and assessed the risk of bias in the included studies according to the Cochrane Handbook, version 5.1.0. Due to great heterogeneity in the choice and reporting of outcome measures and the different durations of follow-up among the studies, this analysis is confined to a qualitative systematic review. RESULTS: Five RCTs involving 591 women were reviewed (treatment group [TG], 292 cases; control group [CG], 299 cases). Generally, the five RCTs exhibited low risk of bias. This study indicated no significant improvement in prolapse symptoms, in quality of life, or in the degree of prolapse for women with POP in the TG compared to those in the CG. CONCLUSIONS: Insufficient evidence was found to support adding perioperative PFMT to surgery over the use of surgery alone in women undergoing surgery for POP. Adequately, powered RCTs with longer follow-up periods are required to evaluate the long-term effect of perioperative PFMT. Neurourol. Urodynam. 35:666-674, 2016. © 2015 Wiley Periodicals, Inc.

Tai chi chuan exercise for patients with breast cancer: a systematic review and meta-analysis.

Objective. Tai Chi Chuan (TCC) is a form of aerobic exercise that may be an effective therapy for improving psychosomatic capacity among breast cancer survivors. This meta-analysis analyzed the available randomized controlled trials (RCTs) on the effects of TCC in relieving treatment-related side effects and quality of life in women with breast cancer. Methods. RCTs were searched in PubMed, Embase, Web of Science, and Cochrane Library through April 2014. Data were analyzed on pathology (pain, interleukin-6, and insulin-like growth factor 1), physical capacity (handgrip, limb physical fitness, and BMI), and well-being (physical, social, emotional, and general quality of life). Results. Nine RCTs, including a total of 322 breast cancer patients, were examined. Compared with control therapies, the pooled results suggested that TCC showed significant effects in improving handgrip dynamometer strength, limb elbow flexion (elbow extension, abduction, and horizontal adduction). No significant differences were observed in pain, interleukin-6, insulin-like growth factor, BMI, physical well-being, social or emotional well-being, or general health-related quality of life. Conclusion. The short-term effects of TCC may have potential benefits in upper limb functional mobility in patients with breast cancer. Additional randomized controlled trials with longer follow-up are needed to provide more reliable evidence.

MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast cancer by targeting the RAB5A.

MiR-130a has been demonstrated to play important roles in many types of cancers. Nevertheless, its biological function in breast cancer remains largely unknown. In this study, we found that the expression level of miR-130a was down-regulated in breast cancer tissues and cells. Overexpression of miR-130a was able to inhibit cell proliferation, invasion and migration in MCF7 and MDA-MB-435 cells. With the bioinformatics analysis, we further identified that RAB5A was a directly target of miR-130a, and its mRNA and protein level was negatively regulated by miR-130a. Immunohistochemistry verified RAB5A was upregulated in breast cancer tissues. Therefore, the data reported here demonstrate that miR-130a is an important tumor suppressor in breast cancer, and imply that miR-130a/RAB5A axis have potential as therapeutic targets for breast cancer.