TREM1/DAP12 based novel multiple chain CAR-T cells targeting DLL3 show robust anti-tumour efficacy for small cell lung cancer.

Small cell lung cancer (SCLC), recognized as the most aggressive subtype of lung cancer, presents an extremely poor prognosis. Currently, patients with small cell lung cancer face a significant dearth of effective alternative treatment options once they experience recurrence and progression after first-line therapy. Despite the promising efficacy of immunotherapy, particularly immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and various other tumours, its impact on significantly enhancing the prognosis of SCLC patients remains elusive. DLL3 has emerged as a compelling target for targeted therapy in SCLC due to its high expression on the membranes of SCLC and other neuroendocrine carcinoma cells, with minimal to no expression in normal cells. Our previous work led to the development of a novel multiple chain chimeric antigen receptor (CAR) leveraging the TREM1 receptor and DAP12, which efficiently activated T cells and conferred potent cell cytotoxicity. In this study, we have developed a DLL3-TREM1/DAP12 CAR-T (DLL3-DT CAR-T) therapy, demonstrating comparable anti-tumour efficacy against SCLC cells in vitro. In murine xenograft and patient-derived xenograft models, DLL3-DT CAR-T cells exhibited a more robust tumour eradication efficiency than second-generation DLL3-BBZ CAR-T cells. Furthermore, we observed elevated memory phenotypes, induced durable responses, and activation under antigen-presenting cells in DLL3-DT CAR-T cells. Collectively, these findings suggest that DLL3-DT CAR-T cells may offer a novel and potentially effective therapeutic strategy for treating DLL3-expressing SCLC and other solid tumours.

Notoginsenoside R1 restrains the proliferation and migration of airway smooth muscle cells isolated from rats with chronic obstructive pulmonary disease.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a common disorder that is characterized by systemic and lung inflammation. Notoginsenoside R1 (NGR1) displays anti-inflammatory properties in numerous diseases. We aimed to explore the function and mechanism of NGR1 in COPD. MATERIALS AND METHODS: COPD rats were established through cigarette smoke exposure, lipopolysaccharide injection, and cold stimulation. Rat airway smooth muscle cells (ASMCs) were separated and identified. Then, ASMCs were treated with NGR1 (25 or 50 µM) and cigarette smoke extract (CSE). Thereafter, the vitality, proliferation, and migration of ASMCs were measured. Additionally, cell cycle, inflammation-related factors, α-SMA, and PI3K/AKT pathway-related marker expressions of the ASMCs were also detected. Molecular docking experiments were conducted to explore the interaction of NGR1 to PI3K, TGF-ß, p65, and AKT. Moreover, 740 Y-P (a PI3K/Akt pathway agonist) were used to validate the mechanism of NGR1 on COPD. RESULTS: NGR1 inhibited the proliferation and migration, but caused cell cycle arrest for CSE-triggered ASMCs. Furthermore, NGR1 not only decreased IL-1ß, IL-6, IL-8, and TNF-α contents, but also reduced α-SMA expression in CSE-stimulated ASMCs. Moreover, NGR1restrainedTGF-ß1 expression, PI3K, p65, and AKT phosphorylation in CSE-stimulated ASMCs. Molecular docking experiments showed NGR1 exhibited a strong binding ability to PI3K, TGF-ß1, p65, and AKT. Notably, the effects of NGR1 on the proliferation and migration of CSE-induced ASMCs were reversed by 740 Y-P. CONCLUSIONS: NGR1 can restrain the proliferation and migration of CSE-induced ASMCs, indicating that NGR1 may be a therapeutic candidate for treating COPD.

Semaphorin4A promotes lung cancer by activation of NF-κB pathway mediated by PlexinB1.

Background: Lung cancer (LC) is the most prevalent cancer with a poor prognosis. Semaphorin4A (Sema4A) is important in many physiological and pathological processes. This study aimed to explore the role and mechanism of Sema4A in LC. Methods: Firstly, Sema4A expression was analyzed by the available dataset and detected in human normal bronchial epithelial cell line (HBE) and LC cell line (NCI-H460). Then, LC cells were transfected with Sema4A siRNA, and the cells were stimulated by PlexinB1, PlexinB2, PlexinD1 blocking antibodies, IgG antibody, BAY 11-7082 (an inhibitor for NF-κB pathway) and Sema4A-Fc protein, alone or in combination. After transfection, PlexinB1 mRNA expression was analyzed. Next, the biological functions, including proliferative, migratory, invasive abilities and viability of the cells were detected by colony formation, scratch, Transwell and MTT assays, respectively. NF-κB, Stat3 and MAPK protein expressions were determined by western blot. Furthermore, the secretion of IL-6 in LC cells was tested by ELISA. Results: Sema4A was highly expressed in LC tissues and cells, could activate the NF-κB pathway and upregulate PlexinB1 mRNA expression. Furthermore, we observed that Sema4A knockdown suppressed the biological functions of NCI-H460 cells, while Sema4A-Fc protein reversed the situation. However, Sema4A-induced biological functions and activation in the NF-κB pathway were inhibited by PlexinB1 blocking antibody. Consistently, Sema4A promoted IL-6 production, which was down-regulated by PlexinB1 blocking antibody and BAY 11-7082. Conclusions: Sema4A may facilitate LC development via the activation of the NF-κB pathway mediated by PlexinB1, suggesting that Sema4A would be a novel therapeutic target for LC treatment.

Chinese expert consensus on the multidisciplinary management of pneumonitis associated with immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICIs) have successfully treated a number of different types of cancer, which is of great significance for cancer treatment. With the widespread use of ICIs in clinical practice, the increasing checkpoint inhibitor pneumonia (CIP) will be a challenge to clinicians. To guide the diagnosis and treatment of CIP, we conducted in-depth discussions based on the latest evidence, forming a consensus among Chinese experts on the multidisciplinary management of CIP.

LncRNA HOTAIR inhibits the progression of fibroblast-like synoviocytes by sponging miRNA-106b-5p in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease of unknown etiology. Human fibroblast-like synoviocytes (HFLSs) are the main effector cells for synovial hyperplasia and invasion in RA. Long non-coding RNAs (lncRNAs) play key roles in several autoimmune diseases, including RA. We investigated the effects of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) on the pathological behavior of HFLSs in RA. The microRNAs (miRNAs) with potential binding sites for lncRNA HOTAIR were predicted using Starbase v2.0. TargetScan (http://www.targetscan.org) was used to analyze the potential target genes of miR-106b-5p. The interactions were further verified using a dual-luciferase reporter assay. RNA and protein expression was determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting. The proliferation, cell invasion and migration, and cell apoptosis of HFLSs in RA was detected by the 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry (FCM). The dual luciferase reporter assay confirmed the interactions between lncRNA HOTAIR and miR-106b-5p and between miR-106b-5p and SMAD family member 7 (SMAD7). The qRT-PCR results indicated that the expression of lncRNA HOTAIR was markedly decreased and that of miR-106b-5p was markedly increased in HFLSs of RA. Cell proliferation, invasion, and migration of HFLSs were inhibited by lncRNA HOTAIR upregulation, and the expression of miR-106b-5p was negatively regulated by lncRNA HOTAIR in HFLSs. Apoptosis of HFLS cells was improved by the overexpression of lncRNA HOTAIR. All the effects of lncRNA HOTAIR upregulation on HFLSs were reversed after the overexpression of miR-106b-5p. Smad7 was identified as a target gene of miR-106b-5p, and the effects of downregulation of miR-106b-5p on HFLSs could be abolished by silencing Smad7. We found that lncRNA HOTAIR was significantly downregulated in the HFLSs of patients with RA. Moreover, lncRNA HOTAIR influenced cell growth, migration, invasion, and apoptosis in HFLSs through the miR-106b-5p/Smad7 axis.

Case Report: Heterogeneity of Resistance Mechanisms in Different Lesions Co-Mediate Acquired Resistance to First-Line Icotinib in EGFR Mutant Non-Small Cell Lung Cancer.

Epidermal growth factor receptor (EGFR)-activating mutations are major oncogenic mechanisms in non-small cell lung cancer (NSCLC). Most patients with NSCLC with EGFR mutations benefit from targeted therapy with EGFR- tyrosine kinase inhibitors (TKIs). One of the main limitations of targeted therapy is that the tumor response is not durable, with the inevitable development of drug resistance. Previous studies demonstrated that the potential resistance mechanisms are diverse, including the presence of EGFR T790M, MET amplification, mesenchymal transformation, and anaplastic lymphoma kinase (ALK) rearrangement. The patient in our report was diagnosed with stage IA lung adenocarcinoma harboring the EGFR L858R mutation and underwent radical surgery. The patient received icotinib for 12 months after recurrence. Subsequent molecular analysis of the left pleural effusion indicated that LCLAT1-ALK fusion might be an underlying mechanism contributing to the acquired resistance to icotinib. Ensartinib was prescribed, but the lesion in the right lung continued to progress. Hence, a re-biopsy and molecular analysis of lesions in the right lung was performed to solve this problem. In contrast to the left pleural effusion, EGFR exon 20 T790M might have mediated the acquired resistance in lesions in the right lung of this patient. The combination of osimertinib and ensartinib has achieved a rapid partial response until now. The complexity and heterogeneity in our case may provide new insights into the resistance mechanisms of targeted therapy.

[Non-surgical local treatment for pulmonary aspergilloma].

Pulmonary aspergilloma (PA) is usually secondary to pulmonary cavities. The main purpose of PA treatment is to prevent life-threatening hemoptysis. Many patients cannot tolerate surgical resection, which is considered the preferred treatment. Oral or intravenous antifungal therapy is less effective because PA usually does not invade the blood vessels of the pulmonary cavity. In this case, arterial embolization, local injection with drugs, and radiation therapy can be considered. This article will summarized various non-surgical local treatments for PA (hemoptysis) to refer clinical decision-making.

A systematic literature review and meta-analysis on the impact of COPD on atrial fibrillation patient outcome.

BACKGROUND: COPD is often accompanied by extra-pulmonary manifestations such as thrombo-embolic and hemorrhagic events, the disease is linked with atrial fibrillation (AF). OBJECTIVE: The objective of the current review was to assess the impact of chronic obstructive pulmonary disease (COPD) on outcomes of atrial fibrillation (AF). METHODS: PubMed, Scopus, Embase, and Web of Science databases were searched for studies comparing overall mortality, cardiovascular death, and other outcomes for AF patients with and without COPD. The data retrieved were subjected to both qualitative and quantitative analyses. The hazard ratios (HR) obtained for mortality in presence of COPD were pooled to meta-analyze using generic inverse variance function of RevMan 5.3 software. The association of various risk factors and HRs were pooled with 95% confidence interval (CI). The quality of the included studies was assessed using Newcastle Ottawa scale (NOS). RESULTS: The hazard ratios (HR) were calculated with 95% confidence intervals (CIs). A total of seven studies were included. The pooled HR for the impact of COPD on overall mortality and cardiovascular mortality in AF patients was found to be 1.70 (95% CI: 1.47, 1.97; p<0.0001) and 1.80 (95% CI: 1.29, 2.52; p = 0.0005), respectively. Hemorrhagic events were significantly higher in AF patients with COPD (Odds ratio (OR): 1.84; 95% CI: 1.58, 2.14; p<0.00001). CONCLUSION: COPD has a deleterious impact on AF progression in terms of overall mortality, cardiovascular death, stroke and hemorrhagic complications.

The emerging regulatory roles of long non-coding RNAs implicated in cancer metabolism.

Compared to normal cells, cancer cells exhibit specific metabolic characteristics that facilitate the growth and metastasis of cancer. It is now widely appreciated that long non-coding RNAs (lncRNAs) exert extensive regulatory effects on a spectrum of biological processes through diverse mechanisms. In this review, we focus on the rapidly advancing field of lncRNAs and summarize the relationship between the dysregulation of lncRNAs and cancer metabolism, with a particular emphasis on the specific roles of lncRNAs in glycolysis, mitochondrial function, glutamine, and lipid metabolism. These investigations reveal that lncRNAs are a key factor in the complexity of malignant cancer metabolism. Only through understanding the relevance between lncRNAs and cancer metabolic reprogramming can we open a new chapter in the history of carcinogenesis, one that promises to alter the methods of cancer diagnosis and treatment.

Radiofrequency Ablation with Continued EGFR Tyrosine Kinase Inhibitor Therapy Prolongs Disease Control in EGFR-Mutant Advanced Lung Cancers with Acquired Resistance to EGFR Tyrosine Kinase Inhibitors: Two Case Reports.

OBJECTIVE: Lung cancer remains the leading cause of malignant tumor-related death globally. There is mounting evidence that a large proportion of patients harboring epidermal growth factor receptor (EGFR) mutation and treated with EGFR TKI experience oligoprogressive disease. The optimal treatment strategy for these patients is undetermined. Thus, in this article, we report two cases of EGFR-mutant NSCLC patients with locally resistant lesions achieving disease control via combination therapy. PATIENTS AND METHODS: We present two cases of lung adenocarcinoma patients that developed oligoprogressive disease during TKI treatment. For further treatment, the patient then received radiofrequency ablation. RESULTS: Through follow-up observation, we found that the addition of radiofrequency ablation might provide the clinical benefit of these two NSCLC patients. CONCLUSION: Our two cases provide a promising treatment for oligoprogressive disease during the first-line EGFR-TKI therapy.

circRNAs and Exosomes: A Mysterious Frontier for Human Cancer.

Exosomes are nano-sized membrane-bound vesicles and contain active substances (DNA, noncoding RNA [ncRNA], protein), which provide a novel method of transferring effector messages between cells. Circular RNAs (circRNAs), a kind of ncRNA, have attracted increasing attention over the last decade given advances in whole-genome and transcriptome sequencing technologies. It has become increasingly clear that circRNAs regulate gene expression through various actions and play diverse roles in many fields of human cancer biology. Notably, several studies reported that circRNAs are enriched in exosomes and that exosomal circRNAs play an important role in cancer biology. Exosomal circRNAs can be taken up by neighboring or distant cells and affect many aspects of physiological and pathological conditions of the recipient cells, potentially promoting cell communication and tumor metastasis. Herein, we briefly review the molecular mechanisms of circRNAs and recent findings regarding exosomal circRNAs, and highlight the specific roles of exosomal circRNAs in human cancer.

Up-regulated long non-coding RNA DUXAP8 promotes cell growth through repressing Krüppel-like factor 2 expression in human hepatocellular carcinoma.

BACKGROUND AND AIM: Long non-coding RNAs (lncRNAs) are implicated as novel factors in tumorigenesis and tumor progression. Although thousands of lncRNAs have been discovered, only a small portion have been functionally determined in hepatocellular carcinoma (HCC). Here, we aimed to comprehensively analyze differentially expressed lncRNAs, evaluate their clinical significance, and explore the functional roles and underlying mechanism in HCC. METHODS: We identified hundreds of lncRNAs which were dysregulated in HCC tissues through performing integrative analyses using the RNA sequencing data and independent gene microarray data from Gene Expression Omnibus and the Cancer Genome Atlas. RESULTS: Dysregulated DUXAP8, LINC01116, LINC01138, and PCAT6 are significantly associated with HCC patients' poor outcomes. Further experimental validation revealed that down-regulation of lncRNA DUXAP8 inhibited HCC cells proliferation and colony formation ability. Mechanistically, DUXAP8 repressed tumor suppressor KLF2 transcription through interacting with histone-lysine N-methyltransferase enzyme enhancer of zeste homolog 2. CONCLUSION: Taken together, our findings can provide a valuable resource of HCC-associated lncRNAs and new insights into the biological functions of lncRNAs in HCC development.

Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer.

BACKGROUND: NSCLC (non-small-cell lung cancer) is the leading cause of cancer-related mortality worldwide. Both epigenetic and genetic changes contribute to the initiation, development and metastasis of NSCLC. Recently, accumulating data have begun to support the notion that long noncoding RNAs (lncRNAs) function as new crucial regulators of diverse biological processes, including proliferation, apoptosis and metastasis, and play crucial roles in tumorigenesis. Nevertheless, further study is warranted to comprehensively determine lncRNAs' functions and potential mechanism. METHODS: In this study, we performed a comprehensive analysis of the lncRNA expression profile of NSCLC using data from TCGA and Gene Expression Omnibus (GEO). PCAT6 expression level in a cohort of 60 pairs of NSCLC tissues using quantitative real-time PCR (qRT-PCR). Additionally, Loss-of-function assays and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. Tumor formation assay in a nude mouse model was performed to verity the role of PCAT6 in NSCLC in vivo. Meanwhile, RIP, ChIP, resue experiment and western blot assays were used to highlights the potential molecular mechanism of PCAT6 in NSCLC. FINDINGS: We identified that an oncogene, PCAT6, was upregulated in NSCLC, and this upregulation was verified in a cohort of 60 pairs of NSCLC tissues. Additionally, the expression level of PCAT6 was correlated with tumor size (P = .036), lymph node metastasis (P = .029) and TNM stage (P = .038). Loss-of-function and gain-of-function assays were used to assess the role of PCAT6 in promoting NSCLC progression. The results revealed that PCAT6 knockdown mitigated NSCLC cell growth by inducing G1-phase cell cycle arrest and apoptosis in vitro and in vivo. Whereas, PCAT6 overexpression could promoted tumor cell growth. Meanwhile, PCAT6 additionally promoted NSCLC cell migration and invasion. Furthermore, mechanistic investigation demonstrated that the oncogenic activity of PCAT6 is partially attributable to its repression of LATS2 via association with the epigenetic repressor EZH2 (Enhancer of zeste homolog 2). Overall, our study highlights the essential role of PCAT6 in NSCLC, suggesting that PCAT6 might be a potent therapeutic target for patients with NSCLC.

Long non-coding RNA 00312 regulated by HOXA5 inhibits tumour proliferation and promotes apoptosis in Non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer. The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported involved in the progression of various tumours, which can be used as diagnostic indicators or antitumour targets. Here, we found that the long non-coding RNA 00312 was down-regulated in paired NSCLC tissues and correlated with poor clinical outcome; decreased linc00312 expression in NSCLC was associated with larger and later stage tumours. Functional experiments showed that linc00312 could inhibit cell proliferation and promote apoptosis in vitro and in vivo. Furthermore, we found that HOXA5 could bind in the promoter of linc00312 and up-regulated the expression of it. Moreover, linc00312 was down-regulated in the plasma of NSCLC patients compared with that of healthy volunteers or other pulmonary diseases patients. Taken together, our findings indicated that linc00312 could be a novel diagnosis biomarker and a promising therapeutic target for NSCLC.

The pseudogene-derived long noncoding RNA SFTA1P is down-regulated and suppresses cell migration and invasion in lung adenocarcinoma.

Pseudogenes were once considered to be genomic fossils without biological function. Interestingly, recent evidence showed that a lot of pseudogenes are transcribed in human cancers, and their alterations contribute to multiple cancer development and progression. It is apparent that many pseudogenes transcribe noncoding RNAs and contribute to the role noncoding genome plays in human cancers. On this basis, some pseudogene transcripts are currently ranked among the classes of long noncoding RNAs. In this study, we identified a new pseudogene-derived long noncoding RNA termed SFTA1P by analyzing the microarray data of non-small cell lung cancer from Gene Expression Omnibus datasets. We found that SFTA1P expression was significantly decreased in non-small cell lung cancer tissues compared with normal tissues in non-small cell lung cancer microarray data. Moreover, decreased SFTA1P expression is only correlated with lung adenocarcinoma patients' poor survival time but not with lung squamous cell carcinoma patients' survival. In addition, gain-of-function studies including growth curves, migration, invasion assays, and in vivo studies were performed to verify the tumor suppressor role of SFTA1P in non-small cell lung cancer. Finally, the potential underlying pathways involved in SFTA1P were investigated by analyzing the SFTA1P-correlated genes in The Cancer Genome Atlas lung adenocarcinoma and normal tissues RNA sequencing data. Taken together, these findings demonstrate that pseudogene-derived long noncoding RNA SFTA1P exerts the tumor suppressor functions in human lung adenocarcinoma. Our investigation reveals the novel roles of pseudogene in lung adenocarcinoma, which may serve as a new target for lung adenocarcinoma diagnosis and therapy.

Circulating long noncoding RNA GAS5 is a novel biomarker for the diagnosis of nonsmall cell lung cancer.

The recently discovered long noncoding RNAs have the potential to regulate many biological processes, which are aberrantly expressed in many tumor types. Our previous study showed that the long noncoding RNA-growth arrest-specific transcript 5 (GAS5) was decreased in lung cancer tissue, which contributed to the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC). GAS5 was also associated with the prognosis of lung cancer patients. These results suggest that GAS5 may represent a novel prognostic indicator and a target for gene therapy in NSCLC. However, the expression and diagnosis significance of GAS5 in the plasma of NSCLC patients was unknown. The plasma samples were more readily available than the tissue samples in clinical, so we designed the study to investigate the diagnosis value of GAS5 in blood samples. In our study, 90 patients with NSCLC and 33 healthy controls were included. Blood samples were collected before surgery and therapy. We extracted the free RNA in the plasma and analyzed the expression of GAS5 with quantitative reverse transcription PCR. Suitable statistics methods were used to compare the plasma GAS5 levels of preoperative and postoperative plasma samples between the NSCLC patients and healthy controls. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic sensitivity and specificity of plasma GAS5 in NSCLC. The results showed that GAS5 was detectable and stable in the plasma of NSCLC patients. Furthermore, the plasma levels of GAS5 were significantly down-regulated in NSCLC patients compared with healthy controls (P = 0.000). Moreover, GAS5 levels increased markedly on the seventh day after surgery compared with preoperative GAS5 levels in NSCLC patients (P = 0.003). GAS5 expression levels could be used to distinguish NSCLC patients from control patients with an area under the curve of 0.832 (P < 0.0001; sensitivity, 82.2%; specificity, 72.7%). The combination of the GAS5 and carcinoembryonic antigen could produce an area of 0.909 under the receiver-operating characteristic curve in distinguishing NSCLC patients from control subjects (95% confidence interval 0.857-0.962, P = 0.000). We have demonstrated that GAS5 expression was decreased in NSCLC Plasma. Plasma samples were more accessible than tissue samples in clinical; therefore, GAS5 could be an ideal biomarker for the diagnosis of NSCLC.

Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis in non-small cell lung cancer.

Long noncoding RNA (lncRNA) plays pivotal roles in cancer development. To date, only a small number of lncRNAs have been characterized at functional level. Here, we discovered a novel lncRNA termed GAS5-AS1 as a tumor suppressor in non-small cell lung cancer (NSCLC). The expression of GAS5-AS1 in NSCLC tumors was much lower than that in the adjacent normal lung tissues. The reduced GAS5-AS1 was significantly correlated with larger tumors, higher TNM stages, and lymph node metastasis in NSCLC patients. While ectopic expression or specific knockdown of GAS5-AS1 had no effect on proliferation, cell cycle progression, and apoptosis, it dramatically decreased or increased, respectively, NSCLC cell migration and invasion. Overexpression of GAS5-AS1 in NSCLC cells reduced a cohort of molecules (ZEB1, N-cadherin, Vimentin, and/or Snail1) critical for epithelial-mesenchymal transition (EMT). Furthermore, the DNA demethylating agent 5-aza-2-deoxycytidine failed to upregulate GAS5-AS1 in NSCLC cells, whereas the pan-HDAC inhibitors panobinostat and SAHA significantly induced GAS5-AS1 in a dose-dependent manner. In addition, GAS5-AS1 can be upregulated by specific knockdown of HDAC1 or HDAC3. Collectively, our data suggest that histone modifications play a major role leading to epigenetic silencing of GAS5-AS1 in NSCLC and subsequently promote tumor metastasis via upregulation of several key EMT markers.

Upregulation of long intergenic noncoding RNA 00673 promotes tumor proliferation via LSD1 interaction and repression of NCALD in non-small-cell lung cancer.

Despite improvements in diagnostics and treatment of non-small cell lung cancer (NSCLC), it remains the leading causes of cancer-related mortality worldwide. In more recent years, mutiple lines of evidence have highlighted long noncoding RNAs (lncRNAs) serve as novel class of regulators of cancer biological processes, including proliferation, apoptosis and metastasis. LncRNAs serve as a novel class of regulators of cancer biological processes in cancer, but little is known of their expression and potential functions in NSCLC. We identified an oncogene, linc00673, whose expression level was upregulated by bioinformatics analyses and qRT-PCR analyses in NSCLC. The effects of linc00673 on tumor progression were investigated in vitro and in vivo. Linc00673 knockdown significantly inhibited cell proliferation and colony-forming ability, and suppressed S-phase entry in vitro and shRNA linc00673 mediated knockdown significantly inhibit tumor growth in vivo, meanwhile, linc00673 overexpression increased tumor cell growth. Analysis of RNAseq data revealed linc00673 could modulate the transcription of a large amount of genes including oncogene and tumor suppressor gene, so we investigated the role and regulatory mechanism of linc00673 in NSCLC proliferation. Further mechanistic analyses indicated that the oncogenic activity of linc00673 is partially attributable to its repression of NCALD through association with the epigenetic repressor LSD1. Taken together, these findings suggested that linc00673 could play crucial role in NSCLC progression and might be a potential therapeutic target for patients with NSCLC.

The growth arrest-specific transcript 5 (GAS5): a pivotal tumor suppressor long noncoding RNA in human cancers.

Long noncoding RNAs (lncRNAs), which refer to a group of RNAs with length more than 200 nucleotides and limited protein-coding potential, play a widespread role in regulating biological processes, such as cell differentiation, proliferation, apoptosis, and migration. LncRNAs are dysregulated in multiple cancers, playing an either oncogenic or tumor-suppressive role. LncRNA GAS5 is a recently identified tumor suppressor involved in several cancers, like breast cancer, prostate cancer, lung cancer, and colorectal cancer. The low-expression pattern confers tumor cells elevated capacity of proliferation and predicts poorer prognosis. Existing studies mirror that lncRNA GAS5 promises to be a novel diagnostic biomarker, therapy target, as well as prognostic biomarker. In this review, we will summarize the current knowledge about this vital lncRNA, from its discovery, characteristics, and biological function to molecular mechanism in various neoplasms.

Pseudogene-expressed RNAs: a new frontier in cancers.

Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in post-genomic biology. Since the completion of the ENCODE (Encyclopedia of DNA Elements) and FANTOM (Functional Annotation of Mammals) project, tens of thousands of pseudogenes as well as numerous long non-coding RNA (lncRNA) genes were identified. However, while pseudogenes were initially regarded as non-functional relics littering the human genome during evolution, recent studies have revealed that they play critical roles at multiple levels in diverse physiological and pathological processes, especially in cancer through parental-gene-dependent or parental-gene-independent regulation. Herein, we review the current knowledge of pseudogenes and synthesize the nascent evidence for functional properties and regulatory modalities exerted by pseudogene-transcribed RNAs in human cancers and prospect the potential as molecular signatures in cancer reclassification and tailored therapy.