Cancer Susceptibility Candidate Research Articles

High CASC expression predicts poor prognosis of lung cancer: A systematic review with meta-analysis.

The long non-coding RNA cancer susceptibility candidate (CASC) has abnormal expression in lung cancer tissues and may correlate with lung cancer prognosis. This study aimed to comprehensively evaluate the association between CASC expression and the cancer prognosis. PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure databases were searched until April 1, 2023, to obtain the relevant literature. Studies that met the predefined eligibility criteria were included, and their quality was independently assessed by 2 investigators according to the Newcastle-Ottawa Scale (NOS) score. Detailed information was obtained, such as first author, year of publication, and number of patients. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted and grouped to assess the relationship between CASC expression and cancer prognosis. The dichotomous data was merged and shown as the odds ratio (OR) with a 95% CI was extracted to assess the relationship between CASC expression and clinicopathological parameters. A total of 12 studies with 746 patients with lung cancer were included in the meta-analysis. The expression levels of lncRNA CASC2 and CASC7 were decreased, while those of CASC9, 11, 15, and 19 were induced in lung cancer tissues compared with paracancerous tissues. In the population with low CASC expression (CASC2 and CASC7), high CASC expression indicated a good lung cancer prognosis (HR = 0.469; 95% CI, 0.271-0.668). Conversely, in the population with high CASC expression (CASC9, 11, 15, and 19), high CASC expression predicted a poor lung cancer outcome (HR = 1.910; 95% CI, 1.628-2.192). High CASC expression also predicted worse disease-free survival (DFS) (HR = 2.803; 95% CI, 1.804-6.319). Combined OR with 95% CI revealed an insignificant positive association between high CASC expression and advanced TNM stage (OR = 1.061; 95% CI, 0.775-1.454), LNM (OR = 0.962; 95% CI, 0.724-1.277), tumor size (OR = 0.942; 95% CI, 0.667-1.330), and histological grade (OR = 1.022; 95% CI, 0.689-1.517). The CASC expression levels negatively correlate with lung cancer prognosis. Therefore, CASC expression may serve as a prognostic marker and a potential therapeutic target for lung cancer.

Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons

AbstractAlzheimer's disease (AD) is a debilitating systemic disorder that has a detrimental impact on the overall well‐being of individuals. Emerging research suggests that long non‐coding RNAs play a role in neural development and function. Nevertheless, the precise relationship between lncRNAs and Alzheimer's disease remains uncertain. The authors' recent discoveries have uncovered an unconventional mechanism involving the regulation of synaptic plasticity and the functioning of the hippocampal fragile X mental retardation protein 1 (FMR1)—neurotrophin 3 (NTF3) pathway, which is mediated by cancer susceptibility candidate 15 (CASC15). Subsequently, functional rescue experiments were performed to illustrate the efficient delivery of exosomes harboring a significant amount of 2610307p16Rik transcripts, which is the murine equivalent of human CASC15, to the hippocampal region of mice. This resulted in significant improvements in synaptic morphological plasticity and cognitive function in APP/PS1 mice. Given the pivotal involvement of CASC15 in synaptic plasticity and the distinctive regulatory mechanisms of the CASC15‐FMR1‐NTF3 axis, CASC15 emerges as a promising biomarker for Alzheimer's disease and may even possess potential as a feasible therapeutic target.

Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA.

This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan-Meier (K-M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.

LncRNA CASC9 enhances the stability of SOCS-1 by combining with FUS to alleviate sepsis-induced liver injury

BackgroundLiver injury plays a major role in the development of sepsis. Liver damage after sepsis is an independent risk factor for multiple organ failure and death. Cancer susceptibility candidate 9 (CASC9) exerts a protective effect on sepsis-induced acute lung injury (ALI). However, the role and underlying mechanism haven’t been fully evaluated. MethodsAnimal and cell models of sepsis were established in vivo and in vitro experiments. The histological and apoptosis analyses of liver tissues were tested by hematoxylin–eosin (HE) staining and terminal dUTP nick end labeling (TUNEL) assay, respectively. Serum levels of inflammatory cytokines were detected via using an enzyme-linked immunosorbent assay (ELISA). The expressions of CASC9, suppressor of cytokine signaling (SOCS)-1, Bcl-2, Bax, Bad, and caspase3 were measured by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to examine cell viability and apoptosis, respectively. RNA immunoprecipitation (RIP) and RNA-pull down assay were used to verify the binding relationships among CASC9, SOCS-1 and FUS. ResultsCASC9 and SOCS-1 were lowly expressed in animal and cell models of sepsis liver injury. CASC9 or SOCS-1 overexpression could inhibit cell apoptosis upon lipopolysaccharide (LPS) induction. Meanwhile, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and IL-8 were reduced by CASC9 or SOCS-1 overexpression in LPS-induced LO2 cells. Mechanistically, CASC9 interacted with fused in sarcoma (FUS) to stabilize the mRNA of SOCS-1. SOCS-1 silencing antagonized the effects of CASC9 on improving sepsis liver injury. ConclusionCASC9 overexpression ameliorated the sepsis-induced liver injury, and the probable underlying mechanism may be that CASC9 stabilized the SOCS-1 mRNA by interacting with FUS.

Long non-coding RNA CASC7 is a promising serum biomarker for hepatocellular carcinoma

BackgroundAt present, a large number of studies have found that long non-coding RNAs (lncRNAs) can be used as biomarkers for diagnosis and monitoring prognosis of hepatocellular carcinoma (HCC). The expression of lncRNA cancer susceptibility candidate 7 (CASC7) in HCC has rarely been studied. The purpose of this study was to explore the expression of CASC7 and its correlation with clinical features, and to further analyze its diagnostic value in HCC.MethodsSerum samples were collected from 80 patients with HCC, 80 patients with chronic hepatitis B (CHB), and 80 healthy people. The expression level of serum CASC7 was detected by droplet digital PCR. Appropriate parametric and nonparametric tests were used for data analysis.ResultsThe results showed that the expression of CASC7 in serum of patients with HCC was significantly higher than that of patients with CHB (median: 8.8 versus 2.2 copies/µl, p < 0.001) and healthy controls (median: 8.8 versus 3.8 copies/µl, p < 0.001). High expression of serum CASC7 was significantly correlated with tumor number (p = 0.005), intrahepatic metastasis (IM) (p < 0.001), tumor size (p = 0.007) and tumor-node-metastasis (TNM) stage (p = 0.008). The area under the curve (AUC) of CASC7 to distinguish HCC patients from CHB patients and healthy controls was 0.808 (95% CI: 0.742–0.874) at the cut-off value of 7.24 copies/µl with 63.8% sensitivity and 95.2% specificity.ConclusionsThis study suggested that CASC7 was significantly up-regulated in serum of patients with HCC and closely related to tumor number, IM, tumor size and TNM stage, which may serve as a promising diagnostic biomarker.

The potential use and experimental validation of genomic instability-related lncRNA in pancreatic carcinoma.

This study explored the potential role of long noncoding RNA (lncRNAs) associated with genomic instability in the diagnosis and treatment of pancreatic adenocarcinoma (PAAD). Transcriptome and single-nucleotide variation data of PAAD samples were downloaded from the cancer genome atlas database to explore genomic instability-associated lncRNAs. We constructed a genomic instability-associated lncRNA prognostic signature. Then gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were used to explore the physiological role of lncRNAs involved in genomic instability. Tumor microenvironments, immunotherapy response, immune cell infiltration, immune checkpoint, and drug sensitivity were compared between high-risk and low-risk groups. In vitro experiments were performed for external validation. Six lncRNAs associated with genomic instability were identified, capable of predicting the prognosis of PAAD. Patients were assigned to low-risk or high-risk groups using these biomarkers, with better or worse prognosis, respectively. The tumor immune score, immune cell infiltration, and efficacy of immunotherapy were worse in the high-risk group. A drug sensitivity analysis revealed the high- and low-risk groups had different half-maximal inhibitory concentrations. The expression of cancer susceptibility candidate 8 was significantly higher in tumor tissues than in normal tissues, while the expression of LYPLAL1-AS1 exhibited an opposite pattern. They may be potential diagnostic or prognostic biomarkers for patients with pancreatic cancer. Genomic instability-associated lncRNAs were explored in this study and predicted the prognosis of PAAD and stratified patients risk in PAAD. These lncRNAs also predicted the efficacy of immunotherapy and potential therapeutic targets in PAAD.

The expression of lncRNAs CASC2, NEAT1, LINC00299 in breast cancer tissues and their relationship with the XBP1 splicing rate in Iranian patients during 2014-2019: A cross-sectional study.

Breast cancer is a leading cause of incidence and mortality in women globally. Identifying new molecular markers can aid in cancer diagnosis, targeted therapy, and treatment monitoring. This study aimed to measure the expression of the X-box binding protein 1 (XBP1) gene, an index of the unfolded protein response (UPR), and long noncoding RNAs (lncRNAs), including Nuclear Enriched Abundant Transcript 1 (NEAT1), Cancer Susceptibility Candidate 2 (CASC2), and Long Intergenic Nonprotein Coding RNA 299 (LINC00299), as possible regulators of the UPR pathway. Total RNA was extracted from 40 samples of breast tumor tissues and their respective controls. The expression level of lncRNAs CASC2, NEAT1, and LINC00299 was quantified using reverse transcription-polymerase chain reaction (RT-PCR). The ratio of the spliced form of XBP1 to its unspliced form (XBP1u) was determined by PCR and electrophoresis. The results showed a 2.8-fold increase in the ratio of XBP1s/u in breast cancer tissues compared to adjacent nonmalignant samples (p < 0.05). Additionally, the level of lncRNAs NEAT1, CASC2, and LINC00299 in breast tumor tissues increased significantly by twofold, 1.5-fold, and 2.3-fold, respectively, compared to adjacent nonmalignant samples (p < 0.05). Based on the association between the expression of lncRNAs CASC2, LINC00299, and NEAT1 and the XBP1s/u ratio, these lncRNAs could be potential regulators of the UPR pathway. Also, CASC2 and NEAT1 genes could be suggested as suitable biomarkers to distinguish cancerous tissue from noncancerous breast tissue due to their significant increase in expression in cancerous samples compared to adjacent noncancerous.

Long noncoding RNA CASC11 suppresses sorafenib-triggered ferroptosis via stabilizing SLC7A11 mRNA in hepatocellular carcinoma cells

As a frontline treatment for patients with advanced hepatocellular carcinoma (HCC), sorafenib is an effective drug approved by the Food and Drug Administration (FDA). Ferroptosis, a newly defined programmed cell death process with the hallmark of the accumulation of iron-dependent lipid peroxides, can be induced by sorafenib treatment. Our previous study identified oncogenic roles of long noncoding RNA (lncRNA) Cancer susceptibility candidate 11 (CASC11) in HCC progression. However, the relationship between CASC11 and sorafenib-induced ferroptosis in HCC remains unclear. In the present study, we aim to investigate the role of CASC11 in sorafenib-induced ferroptosis in HCC cell lines and determine the involved molecular mechanisms. Here, we demonstrated that sorafenib decreased CASCL11 expression. Knockdown of CASC11 enhanced sorafenib-induced ferroptosis, while overexpression of CASC11 exerted the opposite effect in HCC cells. Moreover, CASC11 led to the accumulation of intracellular malondialdehyde (MDA), lipid reactive oxygen species (ROS) and Fe2+ while depleting glutathione (GSH), thereby suppressing sorafenib-induced ferroptosis and cell death. Ferrostatin-1 (Ferr-1), a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by the silence of CASC11 in HCC cells. Mechanistically, CASC11 upregulated the expression of solute carrier family 7 member 11 (SLC7A11) which is critical for ferroptosis inhibition. CASC11 associated with and stabilized SLC7A11 mRNA. In summary, our data revealed, for the first time, that CASC11 inhibits the sorafenib-induced ferroptosis in HCC cells via regulating SLC7A11, providing a new basis for clinical therapeutic strategies for patients with HCC.

Tn antigen promotes breast cancer metastasis via impairment of CASC4.

Breast cancer is one of the most serious and deadly cancers in women worldwide, with distant metastases being the leading cause of death. Tn antigen, a tumor-associated carbohydrate antigen, was frequently detected in breast cancer, but its exact role in breast cancer metastasis has not been well elucidated. Here we investigated the impact of Tn antigen expression on breast cancer metastasis and its underlying mechanisms. The expression of Tn antigen was induced in two breast cancer cell lines by deleting T-synthase or Cosmc, both of which are required for normal O-glycosylation. It showed that Tn-expressing cancer cells promoted epithelial-mesenchymal transition (EMT) and metastatic features as compared to Tn(-) control cells both in vitro and in vivo. Mechanistically, we found that cancer susceptibility candidate 4 (CASC4), a heavily O-glycosylated protein, was significantly downregulated in both Tn(+) cells. Overexpression of CASC4 suppressed Tn-induced activation of EMT and cancer metastasis via inhibition of Cdc42 signaling. Furthermore, we confirmed that O-glycosylation is essential for the functional role of CASC4 because defective O-glycosylated CASC4 (mutant CASC4, which lacks nine O-glycosylation sites) exerted marginal metastatic-suppressing effects in comparison with WT CASC4. Collectively, these data suggest that Tn-mediated aberrant O-glycosylation contributes to breast cancer metastasis via impairment of CASC4 expression and function.

Urinary Long Non-Coding RNA Levels as Biomarkers of Lupus Nephritis.

Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.

Overexpression of CASC19 contributes to tumor progression and predicts poor prognosis after radical resection in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been implicated as functional molecules in hepatocellular carcinoma (HCC) progression. The present research aimed to investigate the levels of LncRNA cancer susceptibility candidate gene 19 (CASC19) in HCC tissues and cell lines and to explore its potential role in the diagnosis and prognosis of HCC. HCC tissues and cell lines were collected to assess the levels of CASC19 by real-time quantitative reverse transcription PCR (RT-qPCR). The prognostic value of CASC19 was evaluated using the Kaplan-Meier method and Cox regression analysis. The functional role of CASC19 in regulating HCC cell proliferation, migration, and invasion was evaluated by Cell Counting Kit-8 (CCK-8) and Transwell analysis. The potential targeted miR-140-5p of CASC19 was confirmed by a dual-luciferase reporter assay. High CASC19 expression positively correlated with tumor size, differentiation, and TNM stage in HCC patients (P < 0.05). Patients with high CASC19 expression have a poorer survival prognosis and are prone to relapse compared to those with low CASC19. miR-140-5p, a target miRNA for CASC19, negatively correlated with CASC19 levels in tumor tissues. Reduced CASC19 levels attenuated cell proliferation, migration, and invasion, but this attenuation was reversed by suppression of miR-140-5p. Up-regulated CASC19 may serve as a biomarker for predicting poor prognosis in HCC patients. In vitro, overexpressed CASC19 promoted the progression of HCC, indicating that CASC19 may be a possible therapeutic target for the treatment of HCC.

LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells.

Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low-density lipoprotein (ox-LDL)-induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox-LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real-time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit-8, flow cytometry, tube formation, and enzyme-linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox-LDL-induced injury of CMECs by binding to HuR and stabilizing HDAC4.

LncRNA CASC19: a novel oncogene involved in human cancer.

Multiple studies have shown that long non-coding RNAs (lncRNAs) play an important role in the occurrence and development of diverse cancers. Cancer susceptibility candidate 19 (CASC19), encoded by chromosome 8q24.21, is a newly discovered lncRNA that contains 324 nucleotides. CASC19 has been found to be significantly overexpressed in different human cancers, such as non-small cell lung carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, clear cell renal cell carcinoma, glioma, cervical cancer, and nasopharyngeal carcinoma. Moreover, dysregulation of CASC19 was closely associated with clinicopathological parameters and cancer progression. CASC19 regulates a variety of cell phenotypes, including cell proliferation, apoptosis, cell cycle, migration, invasion, epithelial-mesenchymal transition, autophagy, and therapeutic resistance. In this study, we review recent studies on the characteristics and biological function of CASC19, as well as its role in human cancers. These findings suggest that CASC19 may be both a reliable biomarker and a potential therapeutic target in cancers.

Long noncoding RNA CASC9 promotes pancreatic cancer progression by acting as a ceRNA of miR‐497‐5p to upregulate expression of CCND1

Pancreatic cancer (PC) is an aggressive malignancy with poor prognosis. Accumulating studies have showed that long non-coding RNA (lncRNA) is a crucial regulator in various tumorigenesis and progression including PC. This research aims to explore the roles and molecular mechanism of lncRNA cancer susceptibility candidate 9 (CASC9) in PC. The expression levels of lncRNA CASC9 and miR-497-5p were evaluated in PC tissues and paired adjacent healthy tissues by quantitative real-time PCR. PC cell lines were transfected with lentivirus targeting lncRNA CASC9, and cells proliferation, migration and invasion tests were conducted. Dual luciferase reporter assays were also carried out to explore the relationship between lncRNA CASC9, miR-497-5p and Cyclin D1 (CCND1). LncRNA CASC9 was significantly up-regulated in PC tissues, while miR-497-5p expression was down-regulated. Down-regulation of lncRNA CASC9 in PC cells can significantly suppress the cell aggressiveness both in vitro and in vivo; moreover, knock-down of miR-497-5p could neutralize this impact. Additionally, the luciferase activity assay has assured that CCND1 was a downstream target of miR-497-5p. LncRNA CASC9 can promote the PC progression by modulating miR-497-5p/CCND1 axis, which is potential target for PC treatment.

Association between the CASC16 rs4784227 polymorphism and breast cancer risk and prognosis in a northeast Chinese Han population.

Breast cancer (BC) poses a serious threat to women worldwide. This research was designed to explore the association between the rs4784227 polymorphism of cancer susceptibility candidate gene 16 (CASC16) and BC susceptibility and prognosis, aiming to provide further information for the early detection of BC and to accelerate comprehensive cancer management. A total of 1,733 subjects were recruited for this case-control study, of which 828 are BC patients and 905 are healthy individuals. The relevance between SNP rs4784227 and BC risk in diverse genetic models was analyzed by using the SNPStats analysis program and was assessed by odds ratios (ORs) and 95% confidence intervals (CIs) using the binary logistic regression model. Pearson's χ 2 test was used to determine the correlation between the polymorphism and clinical characteristics of BC patients. Additionally, univariate survival analysis was performed by the Kaplan-Meier method and log-rank test, and multivariate survival analysis was performed by Cox regression. SNP rs4784227 was significantly associated with susceptibility to BC in the dominant model (CT/TT versus CC, OR = 1.237, 95% CI = 1.012-1.513, P=0.038). The minor allele of SNP rs4784227 was significantly linked to an increased risk of BC (OR = 1.197, 95% CI = 1.022-1.401, P=0.026). In addition, the rs4784227 polymorphism of CASC16 was associated with perineural invasion (P=0.030), menstrual status (P=0.016) and histological grade (P=0.001, P=0.003, P=0.025; respectively) of BC patients. There was no significant association between the genotypes of rs4784227 and disease-free survival (DFS) or overall survival (OS) of breast cancer patients (P>0.05). The rs4784227 polymorphism of CASC16 may affect susceptibility to breast cancer and is associated with perineural invasion, menstrual status and histological grade in BC patients. Additionally, our results could not confirm that this polymorphism was related to breast cancer prognosis.

Long Non-Coding RNA CASC2 Functions as A Tumor Suppressor in Colorectal Cancer via Modulating The miR-18a-5p/BTG3 Pathway.

Reportedly, long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is involved in regulating colorectal cancer (CRC) progression. However, the function and detailed downstream mechanism of CASC2 in CRC progression are not fully elucidated. The aim of the study was to investigate the potential function and molecular mechanism of CASC2 in CRC progression. In this experimental study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to probe CASC2, microRNA-18a-5p (miR-18a-5p) and B cell translocation gene 3 (BTG3) mRNA expression in CRC tissues and cell lines. After CASC2 was overexpressed in Colo-678 and HCT116 cell lines, methylthiazol tetrazolium (MTT) and 5-bromo-2'-deoxyuridine (BrdU) assays were employed to examine the proliferation of CRC cells. Transwell migration and invasion assays were executed to evaluate the metastatic potential of CRC cells. The targeting relationships among CASC2, miR-18a-5p and BTG3 were validated by dual luciferase reporter gene assay. Western blot assay was applied to examine the regulatory effects of CASC2 and miR-18a-5p on BTG3 protein expression. CASC2 was decreased in CRC tissues and cell lines, and its low expression in CRC tissues was associated with larger tumor size and lymph node metastasis. CASC2 overexpression restrained proliferative, migrative and invasive capabilities of CRC cells. CASC2 could function as a molecular sponge for miR-18a-5p and repress the expression of miR-18a-5p. Furthermore, the inhibitory effects of CASC2 on the malignant phenotypes of CRC cells was counteracted by miR-18a-5p mimics. Additionally, CASC2 could positively regulate BTG3 expression via suppressing miR-18a-5p. CASC2 inhibits CRC development by suppressing miR-18a-5p and raising BTG3 expression.

Long non‑coding RNA CASC11 interacts with YBX1 to promote prostate cancer progression by suppressing the p53 pathway.

Prostate cancer (PCa) is one of the principal causes of cancer-related death worldwide. The roles and mechanisms of long non-coding RNA (lncRNA) involved in the development of PCa remain incompletely understood. The present study aimed to investigate the role and mechanism of lncRNA in PCa tumorigenesis. In the present study, lncRNA cancer susceptibility candidate 11 (CASC11) was revealed to be a crucial regulator of PCa progression. The expression profiles of CASC11 in PCa were identified through analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets, and validated in human PCa specimens and cell lines. Gain- and loss-of-function assays were utilized to explore the biological role of CASC11 in PCa initiation and progression. RNA-sequencing, RNA pull-down and RNA immunoprecipitation analyses were used to explore potential mechanisms with which CASC11 may be associated. Rescue experiments were further conducted to confirm this association. The present results revealed that CASC11 was dominantly distributed in the nuclei of PCa cells, and was highly expressed in PCa tissues and cells. Overexpression of CASC11 was markedly associated with increased tumor proliferation and migratory ability. Functionally, decreased proliferation and migration, as well as inhibited xenograft tumor growth, were observed in CASC11-silenced PCa cells, whereas the opposite effects were detected in CASC11-overexpressing cells. Mechanistically, CASC11 promoted progression of the cell cycle and competitively interacted with Y-box binding protein 1 (YBX1) to block the p53 pathway. Given this, poly (β-amino ester) (PBAE)/small interfering RNA-CASC11 (si-CASC11) nanoparticles were applied to inhibit CASC11 expression and enhance the antitumor effect in vivo. The results revealed that PBAE/si-CASC11 nanoparticles augmented the antitumor efficacy of CASC11 knockdown in vivo. In conclusion, the present study suggested that CASC11 may regulate PCa progression and elucidated a novel CASC11/YBX1/p53 signaling axis, providing a potential lncRNA-directed therapeutic strategy particularly for the treatment of patients with PCa.

LncRNA CASC9 activated by STAT3 promotes the invasion of breast cancer and the formation of lymphatic vessels by enhancing H3K27ac-activated SOX4.

Numerous long noncoding RNAs (lncRNAs) are abnormally expressed in breast cancer (BC), but the underlying mechanisms remain large unknown. Here, we aimed to investigate the functions and mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in BC. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to assess gene and protein expression, respectively. The proliferative and metastatic abilities of BC cells were tested by cell counting kit-8 and transwell assays, respectively. The formation of lymphatic vessels was detected by tube formation assay. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were performed to verify molecular interactions. CASC9 was found to be highly expressed in BC tissues and cell lines, and ectopic overexpression was positively associated with tumor volume, TNM stage, and lymph node metastasis. In addition, CASC9 silencing significantly inhibited the proliferation and invasion of BC cells, as well as BC-associated invasion and formation of lymphatic vessels of human dermal lymphatic endothelial cells. Mechanical studies demonstrated that CASC9 could be transcriptionally activated by STAT3 and elevate SOX4 expression by enhancing the acetylation of its promoter region. Our results illustrated that STAT3-activated CASC9 served as a tumor-promoting gene involved in promoting BC invasion and BC-associated formation of lymphatic vessels by upregulating SOX4 through altering H3K27ac level. This finding elucidated a new underlying network of CASC9 in the metastasis of BC.

CASC15 Gene Polymorphisms and Glioma Susceptibility in Chinese Children.

Gliomas are the most common tumors in the central nervous system. The cancer susceptibility candidate 15 (CASC15) gene has been reported to be a susceptibility gene for several types of cancer. No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms (SNPs) on glioma risk. In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility, the first association study in a relatively large sample, which consisted of 171 patients and 228 healthy controls recruited from China, was performed. The contribution of SNPs (rs6939340 A>G, rs4712653 T>C and rs9295536 C>A) to the risk of glioma was evaluated by multinomial logistic regression, based on the calculation of the odds ratio (OR) and 95% confidence interval (CI). In the single locus and combined analysis, it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk. However, in the stratified analysis, a significant decrease in risk of glioma was observed in subjects of <60 months old with the rs4712653 TT genotype, when compared to those with the CC/CT genotype (OR=0.12, 95% CI=0.02-0.91, P=0.041). The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children. However, more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.

Potential of circulating lncRNA CASC2 as a biomarker in reflecting the inflammatory cytokines, multi‐organ dysfunction, disease severity, and mortality in sepsis patients

BackgroundLong noncoding RNA (lncRNA) cancer susceptibility candidate gene 2 (CASC2) inhibits inflammation and multi‐organ dysfunction in various ways. The present study was intended to explore the potency of blood lncRNA CASC2 as a biomarker for sepsis management.MethodsTotally, 184 sepsis patients and 30 healthy controls were enrolled. The reverse transcription‐quantitative polymerase chain reaction was used to detect lncRNA CASC2 expression in peripheral blood mononuclear cell samples from the subjects. Mortality during 28 days was recorded in sepsis patients.ResultsLncRNA CASC2 was decreased in sepsis patients [median (interquartile range [IQR]): 0.473 (0.241–0.773)] by comparison to healthy controls [median (IQR): 1.019 (0.676–1.685)] (p < 0.001). In sepsis patients, lncRNA CASC2 was negatively correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II) (p = 0.001), Sequential Organ Failure Assessment (SOFA) (p < 0.001), SOFA‐respiratory system (p = 0.010), SOFA‐coagulation (p = 0.020), SOFA‐liver (p = 0.019), and SOFA‐renal (p = 0.010) scores, but was not related to SOFA‐nervous (p = 0.466) and SOFA‐cardio vascular system (p = 0.059) scores. Additionally, lncRNA CASC2 was negatively related to tumor necrosis factor‐α (p = 0.024), interleukin (IL)‐1β (p = 0.013), and IL‐17A (p = 0.002), but was not linked to IL‐6 (p = 0.112) or IL‐10 (p = 0.074). Furthermore, lncRNA CASC2 was lower in sepsis deaths [median (IQR): 0.286 (0.166–0.475)] than in survivors [median (IQR): 0.534 (0.296–0.811)] (p < 0.001). Simultaneously, Kaplan–Meier (KM) curve analysis also observed that lncRNA CASC2 was inversely related to accumulating mortality in sepsis patients (p = 0.003). While lncRNA CASC2 could independently predict lower mortality risk.ConclusionCirculating lncRNA CASC2 inadequacy indicates the release of inflammatory cytokines, severe multi‐organ injuries, and increased mortality in sepsis patients.