Long non-coding RNA AGER-1 functionally upregulates the innate immunity gene AGER and approximates its anti-tumor effect in lung cancer.

Little is known about long non-coding RNA (lncRNA) related to innate immunity in lung cancer. The advanced glycosylation end-product specific receptor (AGER) belongs to the immunoglobulin superfamily, and currently, is the only innate immune pattern-recognition receptor whose abnormal expression has been detected in lung cancer. We aimed to explore the lncRNA that is related to AGER and test its effect on lung carcinogenesis. We selected one lncRNA whose chromosome location is in close proximity to AGER namely lnc-AGER-1 (defined as lncAGER). The expression of lncAGER was tested in 276 pairs of lung cancer tissues and adjacent lung normal tissues, and its correlation with lung cancer clinical progress was analyzed. A series of assays were further used to assess the biological function of lncAGER on lung cancer development, tumor immunity and autophagy. LncAGER expression was moderately correlated with AGER expression (r = 0.360, P = 2.15 × 10-18 ) underlying a mechanism that lncAGER upregulates AGER by competitively binding to miRNA-185. LncAGER was significantly down-regulated in 76.4% of lung cancer tissues compared to adjacent normal tissues due to promoter hypermethylation. Over-expression of the lncRNA resulted in significant decreases in proliferation rate, migration ability, colony formation efficiency of lung cancer cells and tumor growth in nude mice. Notably, lncAGER possibly conduced to enhancement of cytotoxic effect of THP1. Additionally, the lncRNA also promoted cell apoptosis by strengthening autophagy. Taken together, these observations suggest that lncAGER has an inhibitory effect on lung cancer development via AGER, which may serve as a target for lung cancer treatment.

Overexpression of lncRNA IGFBP4-1 reprograms energy metabolism to promote lung cancer progression.

BACKGROUND: Reprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified. METHODS: Here, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4-1 (IGFBP4-1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4-1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4-1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR. RESULTS: Our results showed that lnc-IGFBP4-1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues (P < 0.01), and its expression level was significantly correlated with TNM stage (P < 0.01) and lymph node metastasis (P < 0.05). Further investigation showed that overexpression of lnc-IGFBP4-1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4-1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4-1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4-1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4-1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4-1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4-1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4-1. CONCLUSIONS: Taken together, these findings provide the first evidence that lnc-IGFBP4-1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4-1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.

The Usability, Feasibility, Acceptability, and Efficacy of Digital Mental Health Services in the COVID-19 Pandemic: Scoping Review, Systematic Review, and Meta-analysis.

BACKGROUND: After the rapid spread of the novel SARS-CoV-2, the short-term and long-term mental health impacts of the pandemic on the public, in particular on susceptible individuals, have been reported worldwide. Although digital mental health services expand accessibility while removing many barriers to in-person therapy, their usability, feasibility, acceptability, and efficacy require continued monitoring during the initial phase of the pandemic and its aftermath. OBJECTIVE: In this study, we aimed to understand what mental health services are offered, whether they are practical or acceptable, and to what extent digital mental health services are effective in response to the COVID-19 pandemic across high-income and low- and middle-income countries. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guideline. We implemented searches in PubMed (MEDLINE), Embase, PsycINFO, and Cochrane databases for studies that were published between December 2019 and November 2021 and that involved the use of digital mental health services. Two review authors screened, assessed, and extracted studies independently. The protocol was registered on the International Prospective Register of Systematic Reviews. RESULTS: This review identified 7506 articles through database searching. In total, 65 (0.9%) studies from 18 countries with 67,884 participants were eligible for the scoping review. Of the 65 studies, 16 (24.6%) were included in the meta-analysis. A total of 15 (23.1%) studies measured the usability; 31 (47.7%) studies evaluated the feasibility; 29 (44.6%) studies assessed the acceptability; and 51 (78.5%) studies assessed the efficacy. Web-based programs (21/65, 32.3%), videoconferencing platforms (16/65, 24.6%), smartphone apps (14/65, 21.5%), and SMS text messaging (5/65, 7.7%) were the main techniques. Psychotherapy (44/65, 67.7%) followed by psychoeducation (6/65, 9.2%) and psychological support (5/65, 7.7%) were commonly used. The results of the meta-analysis showed that digital mental health interventions were associated with a small reduction in depressive symptoms (standardized mean difference=-0.49; 95% CI -0.74 to -0.24; P<.001) and a moderate reduction in anxiety symptoms (standardized mean difference=-0.66; 95% CI -1.23 to -1.0; P=.02) significantly. CONCLUSIONS: The findings suggest that digital mental health interventions may be practical and helpful for the general population, at-risk individuals, and patients with preexisting mental disorders across high-income and middle-income countries. An expanded research agenda is needed to apply different strategies for addressing diverse psychological needs and develop integrated mental health services in the post-COVID-19 era. TRIAL REGISTRATION: PROSPERO CRD42022307695; https://tinyurl.com/2jcuwjym.

Upregulation of long non-coding RNA RAB1A-2 induces FGF1 expression worsening lung cancer prognosis.

The chromosomal locations of lncRNAs (long non-coding RNAs, lncRNAs) infer their biological functions in cancer. Lnc-RAB1A-2, a Ras-related protein Rab-1A (RAB1A) upstream lncRNA, was chosen for assessment of its impact on lung cancer prognosis in a case-based analysis and investigation of its biological function though a series of functional assays. Lnc-RAB1A-2 was significantly upregulated in 276 lung cancer tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with clinical stage and metastasis status in lung cancer patients. Patients with high expression levels of this lncRNA had a shorter median survival time (16.0 months vs. 23.0 months, P = 0.011 in southern samples; 8.0 months vs. 19.0 months, P = 0.020 in eastern samples; 13.0 months vs. 19.0 months, P = 0.002 in merged samples) and a higher risk of death than those with lower levels (HR = 1.52; 95% CI = 1.01-2.26, in merged samples). Additionally, overexpression of lnc-RAB1A-2 significantly promoted lung cancer cell proliferation in vitro and in vivo. Further analyses using digital gene expression tag profiling revealed that lnc-RAB1A-2 could affect the expression of fibroblast growth factor 1 (FGF1), a gene involved in the PI3K/AKT/mTOR pathway that is largely activated by RAB1A. FGF1 was confirmed to be a down-stream gene of lnc-RAB1A-2. Collectively, our study demonstrated that lnc-RAB1A-2 is associated with poor lung cancer prognosis by promoting lung cancer development.

Association of nsv823469 copy number loss with decreased risk of chronic obstructive pulmonary disease and pulmonary function in Chinese.

It is highly possible that copy number variations (CNVs) in susceptible regions have effects on chronic obstructive pulmonary disease (COPD) development, while long noncoding RNA (lncRNAs) have been shown to cause COPD. We hypothesized that the common CNV, named nsv823469 located on 6p22.1, and covering lncRNAs (major histocompatibility complex, class I, A (HLA-A) and HLA complex group 4B (HCG4B)) has an effect on COPD risk. This association was assessed through a two-stage case-control study, and was further confirmed with COPD and pulmonary function-based family analyses, respectively. The copy number loss (0-copy/1-copy) of nsv823469 significantly decreased risk of COPD compared with normal (2-copy) (OR = 0.77, 95% CI = 0.69-0.85). The loss allele, inducing copy number loss of nsv823469, has a tendency to transmit to offspring or siblings (P = 0.010) and is associated with forced expiratory volume in 1 second (FEV1) (P = 0.030). Furthermore, the copy number loss of nsv823469 in normal pulmonary tissue decreases the expression levels of HCG4B (r = 0.315, P = 0.031) and HLA-A (r = 0.296, P = 0.044). Our data demonstrates that nsv823469 plays a role in COPD and pulmonary function inheritance by potentially altering expression of HCG4B.