[Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma].

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

Long non-coding RNA cancer susceptibility candidate 2 regulates the function of human fibroblast-like synoviocytes via the microRNA-18a-5p/B-cell translocation gene 3 signaling axis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a perennial inflammatory condition. Preliminary research indicated that long non-coding (lnc)RNA cancer susceptibility candidate 2 (CASC2) was downregulated in the serum of RA patients. Our study was designed to reveal the roles of lncRNA CASC2 in RA and the latent mechanisms underlying its role. Bioinformatics method (Starbase) and dual-luciferase reporter assay revealed that microRNA (miR)-18a-5p directly interacted with lncRNA CASC2. Furthermore, lncRNA CASC2 and miR-18a-5p expression in the serum samples of RA patients and healthy controls were measured via reverse transcription-quantitative PCR. Compared with the healthy subjects, lncRNA CASC2 was downregulated, whereas miR-18a-5p was upregulated in patients with RA. Overexpression of lncRNA CASC2 decreased the viability of human fibroblast-like synoviocytes (HFLSs) and induced apoptosis, as revealed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry analyses. Furthermore, the Western blotting assay suggested that Bax was upregulated and Bcl-2 was downregulated in lncRNA CASC2 up-regulated HFLSs. Downregulation of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, matrix metalloproteinase (MMP)1, and MMP3 levels by lncRNA CASC2 up-regulation was determined using enzyme-linked immunosorbent assays (ELISAs). However, HFLSs co-transfected with miR-18a-5p mimic exhibited opposite effects compared with the case for the overexpression of lncRNA CASC2. The aforementioned methods were used to verify that a binding site exists between B-cell translocation gene 3 (BTG3) and miR-18a-5p. The effects of miR-18a-5p inhibitor on HFLSs were reversed by BTG3 silencing. Overall, lncRNA CASC2 alleviated RA by adjusting the miR-18a-5p/BTG3 signaling axis and could serve as a novel therapeutic option for RA.

Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma / 中国医学科学院学报

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

Long non­coding RNA CASC15 facilitates esophageal squamous cell carcinoma tumorigenesis via decreasing SIM2 stability via FTO­mediated demethylation.

Long non­coding RNAs (lncRNAs) are involved in the regulation of esophageal squamous cell carcinoma (ESCC) progression. However, the function and mechanism of lncRNA cancer susceptibility candidate 15 (CASC15) are poorly defined. In the present study, tumor and normal adjacent tissues were collected from 45 patients with ESCC. Expression levels of CASC15, fat mass and obesity­associated (FTO) protein and single­minded 2 (SIM2) were examined via reverse transcription­quantitative PCR and western blot assays. Cell proliferation and apoptosis were evaluated via MTT, flow cytometry and caspase­3 activity assays, respectively. Additionally, an ESCC mouse xenograft model was used to assess the function of CASC15 in vivo. The interaction between FTO and CASC15/SIM2 was analyzed via RNA immunoprecipitation and RNA pull­down assays. The results revealed that CASC15 expression was elevated in ESCC tissues, and patients with ESCC exhibiting high CASC15 expression had a poor prognosis. CASC15­knockdown inhibited ESCC cell proliferation and facilitated apoptosis. Additionally, CASC15­knockdown decreased the growth of ESCC xenograft tumors. CASC15 decreased SIM2 stability via FTO­mediated demethylation. Additionally, FTO loss markedly weakened CASC15­mediated pro­proliferative and anti­apoptotic effects in ESCC cells. SIM2 downregulation weakened the effect of CASC15­knockdown on cell proliferation and inhibited the increase of the apoptotic rate and caspase­3 activity induced by CASC15 depletion in ESCC cells. In conclusion, CASC15 promoted ESCC tumorigenesis by decreasing SIM2 stability via FTO­mediated demethylation.

Overexpression of CASC2 Improves Cisplatin Sensitivity in Hepatocellular Carcinoma Through Sponging miR-222.

The long noncoding RNA cancer susceptibility candidate 2 (CASC2) has been shown to play a crucial role in cancer cell chemoresistance. However, its function and underlying molecular mechanism in hepatocellular carcinoma (HCC) chemoresistance remain unknown. In this study, we used cisplatin (DDP)-resistant HCC cells to investigate CASC2 function and its underlying mechanism. The results demonstrated that CASC2 expression was significantly reduced in HCC tissues and cells, especially in DDP-resistant HCC tissues and cells. Lower CASC2 expression was strongly correlated with shorter survival times in patients with HCC. Functionally, CASC2 overexpression sensitized DDP-resistant Huh7/DDP and SMMC-7721/DDP cells to DDP. Mechanically, CASC2 improved the sensitivity of HCC cells to DDP through sponging miR-222. Taken together, these findings suggested that overexpression of CASC2 overcame DDP resistance in HCC by regulating miR-222 expression, thereby providing a potential therapeutic strategy for overcoming HCC cell chemoresistance.

Effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells through ERK1/2 and ß-catenin signaling pathways.

OBJECTIVES: This study was aimed to investigate the effects of long non-coding RNA (lncRNA) cancer susceptibility candidate 2c (CASC2c) on the proliferation, metastasis and drug resistance of non-small cell lung cancer (NSCLC) cells. METHODS: The expression of CASC2c in NSCLC tissues and cell lines was detected by real-time fluorescence quantitative PCR (RT-qPCR). MTT and Transwell assay were used to determine the proliferation and migration of NSCLC cells in the experimental group and the control group respectively. The drug sensitivity test was used to confirm whether increasing the CASC2c expression level could reverse the resistance of NSCLC cells to the chemotherapy drug cisplatin. The effects of CASC2c on the expression levels of p-ERK1/2 and ß-catenin were detected by western blot. RESULTS: The results of RT-qPCR showed that CASC2c was under-expressed in NSCLC tissues and cells compared with normal adjacent lung tissues cells (p < 0.05). In addition, the CASC2c expression was remarkably correlated with TNM staging, tumor cell differentiation, lymph node metastasis, smoking and other pathological indicators of patients with NSCLC (p < 0.05). MTT and Transwell assay showed that the high-expression of CASC2c significantly reduced the proliferation and migration of NSCLC cells compared to that of the control group (p < 0.05). Western blot assay showed that the high-expressed CASC2c can decrease the expression of phosphorylated-ERK1/2 (p-ERK1/2) and ß-catenin. CONCLUSIONS: CASC2c was low expressed in NSCLC tissues and cells. What's more, it inhibited the proliferation and migration of NSCLC cells by inhibiting the expression of p-ERK1/2 and ß-catenin and reversed NSCLC cells' resistance to the chemotherapy drug cisplatin. Therefore, CASC2c may serve as a new biomarker and therapeutic target in the diagnosis and treatment of NSCLC.

E2F6-mediated lncRNA CASC2 down-regulation predicts poor prognosis and promotes progression in gastric carcinoma.

AIMS: To investigate the potential biological role of E2F6 and its underlying molecular mechanism in gastric carcinoma (GC) progression. MAIN METHODS: The expressions of cancer susceptibility candidate 2 (CASC2), E2F6 and matrix metalloprotein-2 (MMP-2) were measured by quantitative real-time polymerase chain reaction and western blotting. The inhibitory effect of E2F6 on CASC2 was evaluated using luciferase reporter assay. Cell growth was assessed by colony formation assay and cell counting kit-8. Cell invasion and apoptosis were measured by transwell assay and flow cytometry assay, respectively. In vivo tumorigenicity was assessed by tumor xenografts in nude mice. KEY FINDINGS: Our data revealed that CASC2 was downregulated while E2F6 was upregulated in GC tissues and cell lines. Remarkably, lower expression of CASC2 was associated with poor survival in GC patients. E2F6 inhibited the expression of CASC2. Subsequently, reliable data showed that downregulation of E2F6 suppressed the proliferation and invasion, and promoted the apoptosis of GC cells. Furthermore, downregulation of E2F6 decreased the expression of MMP-2 and increased the activity of caspase-3. However, these changes triggered by E2F6 knockdown could be reversed by inhibition of CASC2. Moreover, we also proved that downregulation of CASC2 reverses the effect of E2F6 knockdown on tumor growth in vivo. SIGNIFICANCE: Our data demonstrated that E2F6 could regulate the proliferation, invasion and apoptosis of GC cells via inhibiting the expression of CASC2, suggesting that E2F6/CASC2 axis is another regulator of GC progression.

Long noncoding RNA cancer susceptibility candidate 2 suppresses papillary thyroid carcinoma growth by inactivating the AKT/ERK1/2 signaling pathway.

OBJECTIVES: Cancer susceptibility candidate 2 (CASC2) and long noncoding RNA (lncRNA) have been identified as a tumor suppressor in colorectal, lung, renal, and stomach cancer as well as in patient gliomas, but the function of CASC2 in papillary thyroid carcinoma (PTC) is not yet clear. The present study aimed to explore the effects of CASC2 in PTC. METHODS: The CASC2 expression was measured in PTC samples and normal tissues by using quantitative real-time polymerase chain reaction. The lentiviral vectors were used to establish CASC2 overexpression models in PTC cell lines to determine the effects of CASC2 on cell proliferation, apoptosis, migration, and invasion. A tumor xenograft animal model was used to examine the functions of overexpression CASC2. RESULTS: CASC2 expression was significantly decreased in PTC tumor tissues than adjacent normal tissues. CASC2 downregulation in PTC tissues significantly correlated with the tumor size, the presence of multifocal lesions, and the advanced pathological stage. CASC2 overexpression suppressed the cell proliferation and promoted apoptosis in PTC cell lines and CASC2 overexpression resulted in the inactivation of protein kinase B (PKB/AKT) and extracellular signal-regulated kinases (ERK1/2). The regulatory effects of CASC2 on PTC cell biological behavior were further enhanced by mitogen-activated protein kinase kinase (MEK) inhibitor U0126 or AKT1/2/3 inhibitor MK-2206 2HCl. CASC2 overexpression suppressed tumor growth in PTC cells in xenograft mouse models. CONCLUSION: Our results indicated that CASC2 significantly suppressed tumorigenesis in PTC and CASC2 may serve as a novel prognostic marker or therapeutic target.

Overexpression of cancer susceptibility candidate 2 inhibited progression of hepatocellular carcinoma cells.

OBJECTIVE: Our study was aimed to investigate the effect of cancer susceptibility candidate 2 (CASC2) on the proliferation, cell cycle, apoptosis, and metastasis of hepatocellular carcinoma (HCC) cells. METHODS: CASC2 expression in tumor tissues and HCC cells was tested by quantitative real-time polymerase chain reaction. After manipulating the expression of CASC2 in Hep3B and HepG2 cells, cells viability, including proliferation, apoptosis, cell-cycle distribution, migration, and invasion were examined by colony formation assay, flow cytometry, wound-healing assay, and transwell assay, respectively. The expression levels of proteins associated with the cell cycle and AKT/mTOR pathway were measured by the western blot. Stably transfected HepG2 cells were used to construct nude mice models, and tumorigenesis was evaluated to investigate the in vivo functions of CASC2 in HCC progression. RESULTS: In tissues and cells of HCC, decreased CASC2 expressions were confirmed. Overexpression of CASC2 made cell cycle stagnated at G0/G1 phase and induced apoptosis. Meanwhile, the overexpression of CASC2 played significant roles in inhibiting the proliferation, migration, and invasion of HCC cells. Furthermore, In vivo experiment indicated that CASC2 restrained the growth of tumors. CONCLUSION: Our study suggested that CASC2 promoted cell apoptosis and suppressed cell growth and metastasis in HCC, indicating that CASC2 might be a useful biomarker of HCC.

LncRNA CASC2 inhibits proliferation and migration of adenocarcinoma cells via miR-4735-3p and mTOR.

Lung adenocarcinoma is a major form of non-small-cell lung cancer that frequently strikes nonsmokers. The disease is often diagnosed at a late stage and the 5-year survival rate is very low. Although previous studies found many somatic alterations associated with lung adenocarcinoma, the molecular basis of the development and progression of the disease is not well understood. We found that long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a putative tumor suppressor, was downregulated in both patient adenocarcinoma tissues and cultured lung cancer cells. Its tumor suppression function seemed to be dependent on its binding to miR-4735-5p. Changing the levels of CASC2 and miR-4735-3p in the cultured adenocarcinoma cells could affect the malignant phenotypes as well as growth of tumors derived from the cells injected into nude mice. Furthermore, the lncRNA and miR-4735-3p interplay likely the suppressed tumor growth through the downstream mammalian target of rapamycin signaling pathway. The results have revealed molecular details that may be critical for the development of lung adenocarcinoma, opening opportunities for the development of novel, and therapeutic tools.

Expression of cancer susceptibility candidate 2 in hepatocellular carcinoma and its influence on the prognosis of the patients / 中华肝胆外科杂志

Objective To investigate the correlations between expression of CASC2 and hepatocellular carcinoma(HCC) prognosis.Methods A total of 129 patients including 80 males and 49 females with HCC were includedin this study,ranging from 21 to 73 years in Xuanwu Hospital of Capital Medical University and Beijing You'an Hospital were retrospectively analyzed from September 2007 to January 2014.Expression of CASC2 was assessed using reverse transcription quantitative-polymerase chain reaction in HCC tissue and the adjacent normal tissue.The correlations between CASC2 mRNA level and clinicopathological parameters was investigated.The relationship between the expression of CASC2 and the prognosis of patients with HCC was analyzed by Kaplan-Meier method.A log-rank analysis was performed to identify group differences.Univariate and multivariate Cox analysis were used to analyze the variables affecting the patient's prognosis.Results In 129 HCC samples,the level of CASC2 expression (0.84 ± 0.05) was lower than (3.35 ± 0.11) adjacent normal tissue (P ＜ 0.05).There were significant differences between CASC2 expression and tumor size,histological differentiation,and tumor stage in 129 HCC speciments.The median expression level of CACS2 in HCC tissues,0.84-fold,was used as the cut-off value to divide the 129 patients into two groups:low-expression group (n =72) and high-expression group (n =57).Overall survival rate of HCC patients with high CACS2 expression was significantly higher than those of patients with low CACS2 expression(P ＜0.05).Multivariate analysis indicated that histological differentiation (HR =0.20,95％ CI:0.05 ～ 0.59),tumor stage (HR =1.71,95％ CI:1.02 ～ 2.99) and CACS2 expression (HR =O.51,95％ CI:O.08 ～0.92) were an independent predictor of overall survival.Conclusion Low expression of CACS2 might be associated with the occurrence and development of HCC.

Effect of CASC2a on proliferation and migration of papillary thyroid carcinoma cells via NF-κB signaling pathway / 医学研究生学报

Objective There are few reports on the relationship between lncRNA cancer susceptibility candidate gene 2 (CASC2) and NF-κB signaling pathway in thyroid papillary carcinoma cells at home and abroad. This study aimed to investigate the effect of lncRNA CASC2a on the proliferation and migration of TPC-1 via NF-κB signaling pathway. Methods TPC-1 was selected and constructed into lncRNA CASC2a overexpression plasmids which were divided into plasmid group [transfection with overexpressed plasmid pcDNA3.1(+)-CASC2a], empty group [transfection with equal amount of pcDNA3.1 (+) empty plasmid], blank group (without any processing). The effect of overexpressed lncRNA CASC2a on the expression of CASC2a in each group of TPC-1 cells was examined. The cells of transfected plasmid group were randomly divided into transfection group [transfection with only overexpressed plasmid pcDNA3.1(+)-CASC2a], transfection + PMA group [transfection with overexpressed plasmid pcDNA3.1(+)- CASC2a + propylene glycol methyl ether acetate (PMA) stimulation], control group (without any processing), PMA group (only plus PMA stimulation). The effects of lncRNA CASC2a on cell proliferation and migration were verified by CCK-8 and cell scratch assays at 24, 48, 72 and 96 h. Western blot was used to detect the expression of p105/p50 and p65 in NF-κB signaling pathway. The expression of NF-κB signaling pathway-related antibody proteins p105/p50 and p65 was observed by NF-κB signaling pathway agonist PMA(propylene glycol methyl ether acetate). Results After transfection with overexpressed plasmid pcDNA3.1(+)-CASC2a, the expression of CASC2a in plasmid group was significantly higher than that in empty group (P<0.05). The cell proliferation ability (0.191±0.005) was significantly lower in transfection+PMA group than that in transfection group (0.217±0.013), PMA group (0.247±0.009), and control group (0.260±0.004), and the difference was statistically significant ( P<0.01), while the cell proliferation ability in transfection group was significantly lower than those in PMA group and control group (P<0.01). The cell migration ability of transfected + PMA group [(0.208±0.109)%] was lower than that of transfection group, PMA group, and control group [(1.775±0.061)%, (1.622±0.519)%, (2.927±0.136)%], while the cell migration ability of transfection group and PMA group was lower than that in control group (P<0.05). The relative expression of p105/p50 and p65 protein in plasmid group was significantly lower than that in blank group (P<0.05). The expression of p105/p50 and p65 protein in transfection+PMA group [(0.674±0.007), (0.713±0.014)] was significantly higher than that in transfection group [(0.581±0.003), (0.570±0.012)] (P<0.05). Conclusion lncRNA CASC2a may inhibit the proliferation and migration of thyroid papillary carcinoma cells through NF-κB signaling pathway.

Down-regulation of CASC2 contributes to cisplatin resistance in gastric cancer by sponging miR-19a.

Increasing evidence suggests the involvement of long non-coding RNAs (lncRNAs) in chemoresistance of cancer treatment. However, their function and molecular mechanisms in gastric cancer chemoresistance are still not well elucidated. In the present study, we investigate the functional role of lncRNA cancer susceptibility candidate 2 (CASC2) in cisplatin (DDP) resistance of gastric cancer and discover the underlying molecular mechanism. Results revealed that CASC2 was decreased in DDP-resistant gastric cancer tissues and cells. Gastric cancer patients with low CASC2 expression levels had a poor prognosis. CASC2 overexpression enhanced DDP sensitivity of BGC823/DDP and SGC7901/DDP cells. Conversely, CASC2 knockdown weakened the response of BGC823 and SGC7901 to DPP. Moreover, CASC2 could function as a miR-19a sponge. miR-19a inhibition could overcome DDP resistance in BGC823/DDP and SGC7901/DDP cells, while miR-19a overexpression led to DDP resistance in BGC823 and SGC7901 cells. Notably, miR-19a overexpression counteracted CASC2 up-regulation-mediated enhancement in DDP sensitivity of BGC823/DDP and SGC7901/DDP cells. On the contrary, the inhibitory effect of CASC2 knockdown on the sensitivity of BGC823 and SGC7901 cells to DDP was reversed by miR-19a inhibition. In summary, CASC2 overexpression overcame DDP resistance in gastric cancer by sponging miR-19a, providing a novel therapeutic target for gastric cancer chemoresistance.

Low Expression of LncRNA Cancer Susceptibility Candidate 2 and its Clinical Significance in Cancer Tissues.

BACKGROUND/AIMS: Long noncoding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is downregulated in various cancers and involved in both tumorigenesis and progression. The aim of this study was to assess the prognostic value of lncRNA CASC2 in cancer patients. METHODS: We searched the Web of Science, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and the Wanfang database to identify studies evaluating the prognostic value of lncRNA CASC2 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. RESULTS: A total of eight studies were included. The combined results showed that lncRNA CASC2 was significantly associated with decreased overall survival (OS) (HR = 0.37, 95% CI, 0.27-0.46, P < 0.001). Subgroup analyses further indicated that low expression of lncRNA CASC2 predicted decreased OS in cancer patients. Additionally, low CASC2 expression levels in cancer tissues appeared to be correlated with advanced clinical staging (OR = 3.32, 95% CI, 2.29-4.80, P < 0.001). CONCLUSIONS: Low CASC2 expression appears to be predictive of poor OS and advanced tumor stage in multiple cancers. CASC2 expression may serve as unfavorable prognostic factor for clinical outcomes in cancer patients.

Evaluation of miR-21 Inhibition and its Impact on Cancer Susceptibility Candidate 2 Long Noncoding RNA in Colorectal Cancer Cell Line.

BACKGROUND: Both microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been shown to have a critical role in the regulation of cellular processes such as cell growth and apoptosis, as well as cancer progression and metastasis. lncRNAs are aberrantly expressed in many diseases including cancer. Although it is well known that miRNAs can target a large number of protein-coding genes, little is known whether miRNAs can also target lncRNAs. In the present study, we determine whether miR-21 can regulate lncRNA cancer susceptibility candidate 2 (CASC2) in colorectal cancer. MATERIALS AND METHODS: LS174T cells were transfected with locked nucleic acid (LNA)-anti-miR-21 and scrambled LNA for 24, 48 and 72 h. The expression of miR-21 and lncCASC2 was evaluated by quantitative reverse transcriptase polymerase chain reaction. RESULTS: However, contrary to what we expected and reported by others, lncCASC2 quantity was significantly reduced in LNA treated LS174T cells compared to the scrambled treated and normal untreated cells (P < 0.05). CONCLUSION: The interaction of miRNA and lncRNA are not as simple as suggested by other reports. Moreover, it could be complex molecular mechanisms underlying the communication of various noncoding RNA elements.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.