Cancer Susceptibility 19 Research Articles

CASC19 Expression in Epithelial Ovarian Cancer Patients and Its Effect on Cancer Cell Proliferation, Invasion and Apoptosis

Objective: It is well documented that long non-coding RNAs are vital in ovarian cancer (OC) occurrence and progression. The purpose of this study is to figure out the function of cancer susceptibility 19 (CASC19) in epithelial ovarian cancer (EOC), as well as its molecular mechanism. Methods: qRT-PCR was applied to determine CASC19 level in EOC tissues, serum and OC cells, and cell function tests to detect cell proliferation, migration and apoptosis. The impact of CASC19 on OC growth was determined by tumor allotransplantation. Results: CASC19 showed high expression in EOC tissues and serum, and OC cells. Patients with high expression had poor prognosis. CASC19 knockout could block OC cell malignant phenotypes in vitro, and its over-expression could reverse the above results. The tumor growth of nude mice was inhibited by CASC19 knockout. Conclusion: CASC19 is highly expressed in EOC patients. CASC19 knockdown can inhibit OC cell proliferation and invasion, and induce apoptosis, which is a promising therapeutic target for EOC.

CASC2 inhibits the growth, migration, and invasion of thyroid cancer cells through sponging miR-18a-5p/FIH1 axis.

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH-1) was potentially targeted by miR-18a-5p, which was confirmed by luciferase reporter assay. Upregulation of FIH-1 abrogated the promotive effect of miR-18a-5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR-18a-5p, thereby regulating the expression of FIH-1. These data elucidated the CASC2/miR-18a-5p ceRNA network in thyroid cancer pathogenesis.

Long non‑coding RNA CASC19 promotes glioma progression by modulating the miR‑454‑3p/RAB5A axis and is associated with unfavorable MRI features.

Glioma is one of the most common malignancies of the nervous system. Long non‑coding RNAs (lncRNAs) are regulators involved in the progression of tumors. The present study aimed to determine the role of lncRNA cancer susceptibility 19 (CASC19) in glioma and its underlying molecular mechanism. Reverse transcription‑quantitative PCR was performed to detect CASC19 and microRNA (miR)‑454‑3p expression in glioma and normal brain tissues. Ras‑related protein in brain 5A (RAB5A) expression in glioma cells was also analyzed via western blotting. The relationship between CASC19 expression, clinicopathological parameters and MRI characteristics in patients with glioma was analyzed. Cell Counting Kit‑8, BrdU, wound healing and Transwell assays were adopted to detect glioma cell proliferation, migration and invasion, respectively. The dual‑luciferase reporter gene and RNA immunoprecipitation experiments were conducted to verify the targeting relationship between CASC19 and miR‑454‑3p, and between miR‑454‑3p and RAB5A. The results revealed that CASC19 expression was significantly upregulated in glioma tissues and cell lines. CASC19 expression was also positively associated with tumor diameter and pathological grade. Additionally, its high expression was closely associated with tumor MRI signal heterogeneity and peritumoral edema. CASC19 upregulation promoted glioma cell proliferation and metastasis, while CASC19‑knockdown demonstrated the opposite effect. CASC19 sponged miR‑454‑3p, which indirectly increased RAB5A expression. The results demonstrated that the CASC19/miR‑454‑3p/RAB5A axis is involved in the promotion of glioma progression.

LncRNA CASC19 contributed to the progression of pancreatic cancer through modulating miR-148b/E2F7 axis.

Cancer susceptibility 19 (CASC19), a crucial lncRNA associated with multiple cancers, has been reported to play a vital role in the progression of human malignant tumors. However, the underlying mechanism of CASC19 in pancreatic cancer (PC) was still unknown. The purpose of this study was to explore the biological and clinical significance of CASC19 in PC. RT-qPCR assay was adopted to analyze CASC19 expression in PC tissues and cell lines. Furthermore, the correlation between the CASC19 level and the survival rate of PC patients was assessed by Kaplan-Meier analysis. Bioinformatics analysis and Luciferase reporter assay were utilized to confirm the interaction between miR-148b and CASC19 or E2F7. Cell viability, migration, invasion, and apoptosis were analyzed using MTT, transwell, and TUNEL assays. The results elucidated that CASC19 expression was markedly increased in PC tissues and cell lines. Patients with high expression of CASC19 had a short survival time. Silencing of CASC19 attenuated PC cell proliferation, migration, and invasion. Moreover, we identified that miR-148b was a target of CASC19. CASC19 was negatively correlated with miR-148b and positively correlated with E2F7. The inhibitory effect of CASC19 knockdown on the progression of PC was reversed by the down-regulation of miR-148b or up-regulation of E2F7. These results demonstrated that CASC19 participated in the development of PC. The CASC19/miR-148b/E2F7 axis might be a new study direction for PC treatment.

Long non-coding RNA CASC19 facilitates non-small cell lung cancer cell proliferation and metastasis by targeting the miR-301b-3p/LDLR axis.

Non-small cell lung cancer (NSCLC) is a lethal tumor resulting in a large number of cancer-related deaths globally. Long noncoding RNAs (lncRNAs) may modulate tumor initiation and metastasis. Although dysregulation of lncRNA cancer susceptibility 19 (CASC19) is validated in NSCLC, further exploration of the CASC19-regulated mechanism in NSCLC is still needed. CASC19 expression was examined in NSCLC cells by a quantitative reverse transcriptase-polymerase chain reaction. The specific role of CASC19 in NSCLC was analyzed by cell counting kit-8, EdU, Transwell and western blot assays. The interaction between miR-301b-3p and CASC19 or low-density lipoprotein receptor (LDLR) was confirmed by luciferase reporter and RNA immunoprecipitation assays. CASC19 is markedly overexpressed in NSCLC. Its deficiency impairs cell proliferation, as well as metastasis in NSCLC. Molecular mechanism experiments indicated that CASC19 negatively modulates the expression of miR-301b-3p and miR-301b-3p can bind with CASC19 in NSCLC. In addition, miR-301b-3p binds to LDLR to impair its expression in NSCLC. Finally, rescue experiments showed that miR-301b-3p inhibition or LDLR overexpression counteracted the CASC19 knockdown-mediated function on cell proliferation and metastasis in NSCLC. CASC19 facilitates NSCLC cell proliferation and metastasis by targeting the miR-301b-3p/LDLR axis, offering a possible strategy for lncRNA-targeted treatment in NSCLC.

Comprehensive analysis of long non-coding RNA and mRNA expression profile in rectal cancer.

Background:Rectal cancer (RC) is a malignant tumor that seriously threatens human health. Long non-coding RNAs (lncRNAs) play a vital role in tumor regulation. Nevertheless, their exact expression features and functions remain obscure, and therefore was the aim of the current study.Methods:We utilized the Affymetrix human GeneChip to screen differentially expressed profiles of lncRNAs and mRNAs from the cancer tissues and matched paracancer tissues of 6 RC patients. Gene Ontology (GO) and pathway enrichment analyses identified crucial functions and pathways of the aberrantly expressed mRNAs. We used quantitative real-time polymerase chain reaction to verify the significant expression differences of 11 candidate lncRNAs between the cancer and paracancer tissues. LncRNA-mRNA coexpression networks were built by calculating the Pearson correlation value to identify significant correlation pairs. Online bioinformatics tools GEPIA2, ONCOMINE, and PROGgeneV2 were used to mine the expression and prognosis of three crucial mRNAs and six verified lncRNAs. Competing endogenous RNA networks were constructed by predicting microRNA response elements and calculating free energy.Results:We found 1658 differentially expressed lncRNAs (778 up-regulated and 880 down-regulated) and 1783 aberrantly expressed mRNAs (909 up-regulated and 874 down-regulated). GO and pathway enrichment analyses revealed the vital functions of the differentially expressed mRNAs, including cell proliferation, cell migration, angiogenesis, and cellular response to zinc ion. The canonical signaling pathways mainly included the interleukin-17, cell cycle, Wnt, and mineral absorption signaling pathways. Six lncRNAs including AC017002.2 (P = 0.039), cancer susceptibility 19 (CASC19) (P = 0.021), LINC00152 (P = 0.013), NONHSAT058834 (P = 0.007), NONHSAT007692 (P = 0.045), and ENST00000415991.1 (P = 0.045) showed significant differences in expression levels between the cancer tissue and paracancer tissue groups. AC017002.2, NONHSAT058834, NONHSAT007692, and ENST00000415991.1 have not yet been reported in RC. The crucial mRNAs myelocytomatosis viral oncogene (MYC), transforming growth factor beta induced (TGFBI), and solute carrier family 7 member 5 (SLC7A5) were selected. AC017002.2 and LINC00152 were positively correlated with MYC, TGFBI, and cytochrome P450 family 2 sub-family B member 6 (All r > 0.900, P < 0.050). NONHSAT058834 was positively associated with MYC (r = 0.930, P < 0.001), and CASC19 was positively correlated with SLC7A5 (r = 0.922, P < 0.001).Conclusion:This study offers convincing evidence of differentially expressed lncRNAs and mRNAs as potential biomarkers in RC.

Long Non-Coding RNA CASC19 Sponges microRNA-532 and Promotes Oncogenicity of Clear Cell Renal Cell Carcinoma by Increasing ETS1 Expression.

PurposeThe long non-coding RNA cancer susceptibility 19 (CASC19) is recognized as an important regulator in gastric cancer, colorectal cancer, and non-small cell lung cancer. Nevertheless, to the best of our knowledge, the expression status and detailed roles of CASC19 in clear cell renal cell carcinoma (ccRCC) have not been elucidated. Hence, we aimed to determine CASC19 expression in ccRCC and investigate its roles in ccRCC oncogenicity. The molecular mechanisms underlying CASC19 functions in ccRCC were also determined.MethodsCASC19 expression was measured by using reverse transcription-quantitative polymerase chain reaction. The effects of CASC19 on ccRCC cell proliferation, colony formation, migration, and invasiveness in vitro, as well as on tumor growth in vivo, were examined by the MTT assay, colony formation assay, cell migration and invasiveness assays, and tumor xenograft in nude nice, respectively.ResultsCASC19 was overexpressed in ccRCC tissues and cell lines. High expression of CASC19 was closely associated with unfavorable clinicopathological parameters and predicted negative clinical outcomes in patients with ccRCC. Knockdown of CASC19 decreased ccRCC cell proliferation, colony formation, migration, and invasiveness, as well as attenuated tumor growth in vivo. Mechanistically, CASC19 functioned as a competing endogenous RNA and upregulated the expression of ETS proto-oncogene 1 (ETS1) through sponging microRNA-532 (miR-532). Furthermore, rescue assays revealed that inhibiting miR-532 or restoring ETS1 expression partially abolished the impacts of CASC19 knockdown on ccRCC cells.ConclusionThe CASC19/miR-532/ETS1 regulatory pathway is crucial for the malignant manifestations of ccRCC, which makes it an attractive target for potential treatments of ccRCC.

MiR93-5p inhibits chondrocyte apoptosis in osteoarthritis by targeting lncRNA CASC2

BackgroundIt has been reported that miR-93-5p and long non-coding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) play opposite roles in regulating chondrocyte apoptosis, indicating the possible interaction between them. This study aimed to investigate the interaction between miR-93-5p and lncRNA CASC2 in chondrocyte apoptosis, which plays critical roles in osteoarthritis (OA).MethodsThe interaction between CASC2 and miR-93-5p was analyzed by dual luciferase assay and overexpression experiments. Levels of CASC2 and miR-93-5p in plasma sample from OA patients and healthy controls were measured by RT-qPCR. The roles of CASC2 and miR-93-5p in regulating the apoptosis of chondrocyte induced by LPS were analyzed by cell apoptosis assay.ResultsThrough bioinformatics analysis we observed the potential interaction between CASC2 and miR-93-5p, which was confirmed by dual luciferase assay. In OA patients, miR-93-5p was downregulated, while CASC2 was upregulated, and they were inversely correlated. LPS treatment led to downregulated miR-93-5p and upregulated CASC2. Overexpression of miR-93-5p led to the downregulated CASC2 in chondrocytes. Under LPS treatment, CASC2 overexpression promoted the apoptosis of chondrocyte. MiR-93-5p overexpression played an opposite role and attenuated the effects of CASC2 overexpression.ConclusionMiR-93-5p was downregulated in OA may inhibit LPS-induced chondrocyte apoptosis by targeting lncRNA CASC2.

Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/\u03b2-catenin signaling pathway

PurposeLong non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells.MethodsThis study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell.ResultsIn the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells.ConclusionThe lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

Long non-coding RNA CASC19 is associated with the progression and prognosis of advanced gastric cancer.

Evidence indicates that aberrantly expressed long non-coding RNAs (lncRNAs) are involved in the development and progression of advanced gastric cancer (AGC). Using RNA sequencing data and clinical information obtained from The Cancer Gene Atlas, we combined differential lncRNA expression profiling and weighted gene co-expression network analysis to identify key lncRNAs associated with AGC progression and prognosis. Cancer susceptibility 19 (CASC19) was the top hub lncRNA among the lncRNAs included in the gene module most significantly correlated with AGC’s pathological variables. CASC19 was upregulated in AGC clinical samples and was significantly associated with higher pathologic TNM stage, pathologic T stage, lymph node metastasis, and poor overall survival. Multivariable Cox analysis confirmed that CASC19 overexpression is an independent prognostic factor for overall survival. Furthermore, quantitative real-time PCR assay confirmed that CASC19 expression in four human gastric cancer cells (AGS, BGC-823, MGC-803, and HGC-27) was significantly upregulated compared with human normal gastric mucosal epithelial cell line (GES-1). Functionally, CASC19 knockdown inhibited GC cell proliferation and migration in vitro. These findings suggest that CASC19 may be a novel prognostic biomarker and a potential therapeutic target for AGC.

Functional role of long non-coding RNA CASC19/miR-140-5p/CEMIP axis in colorectal cancer progression in vitro.

BACKGROUNDLong non-coding RNAs (lncRNAs) are widely involved in tumor regulation. Nevertheless, the role of the lncRNA cancer susceptibility 19 (CASC19) in colorectal cancer (CRC) has yet to be fully clarified.AIMTo explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODSCASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR (qRT-PCR). CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay. In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTSCASC19 expression was markedly upregulated in CRC tissues and CRC cell lines (P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC (P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion, migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1 (CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5p reversed the effect of CASC19 on cell proliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSIONCASC19 positively regulates CEMIP expression through targeting miR-140-5p. CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.

Long non-coding RNA CASC2 in solid tumors: A meta-analysis

Background and aimRecently, several studies have reported that the long non-coding RNA cancer susceptibility 2 (CASC2) is downregulated in human solid tumors. However, as the sample size in those studies was limited, the role of CASC2 in cancer remains unknown. Accordingly, we conducted this meta-analysis to explore the role of CASC2 in solid tumors. MethodsWe systematically searched the PubMed, Medline, Cochrane Library, Web of Science, EMBASE, Ovid, Chinese CNKI, and Chinese WanFang databases. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were used to evaluate the relation between CASC2 and the clinicopathological characteristics and prognosis of patients with cancer. Additionally, we also use The Cancer Genome Atlas (TCGA) dataset to analyze CASC2 expression. ResultsA total of 15 studies with 1158 patients were included in this meta-analysis. The pooled results demonstrated that the expression of CASC2 was related to tumor size (large vs. small: OR = 0.40, 95% CI = [0.30, 0.52]), differentiation (low vs. high+ moderate: OR = 0.42, 95% CI = [0.29, 0.62]) and TNM stage (I + II vs. III + IV: OR = 2.74, 95% CI = [2.08, 3.60]), but not to age, gender and differentiation. High CASC2 expression indicated better overall survival (OS) (HR = 0.41, 95% CI = [0.32, 0.50]) and disease-free survival (DFS) (HR = 0.48, 95% CI = [0.26, 0.66]). Additionally, similar results were obtained through analysis of the TCGA data set. Moreover, it was determined that CASC2 could be an independent predictive factor for OS (HR = 0.38, 95% CI = [0.22, 0.54]) in patients with cancer. ConclusionThis analysis revealed that low CASC2 expression was correlated with advanced clinicopathological characteristics of cancer tumors, and CASC2 may thus be a potential prognostic biomarker in human cancer. However, more studies are needed to further corroborate these findings.

Overexpression of long non-coding RNA cancer susceptibility 2 inhibits cell invasion and angiogenesis in gastric cancer.

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) were aberrantly expressed and acted as key regulators in various types of disease, including cancer. lncRNA cancer susceptibility 2 (CASC2) has been found to be downregulated and acts as a tumor suppressor in various type of cancer, including gastric cancer (GC). However, the precise function of lncRNA CASC2 in GC remains unclear. In the present study, the expression level of lncRNA CASC2 in GC was investigated and the molecular mechanisms by which CASC2 acted as a tumor suppressor in this disease were elucidated. It was found that the expression level of lncRNA CASC2 was decreased, which correlated with TNM stages, vessel invasion, metastasis, and overall survival of patients with GC. Furthermore, overexpression of CASC2 inhibited the invasion and angiogenesis of GC cells. Thus, the present study indicated the important roles and underlying molecular mechanisms of lncRNA CASC2 on GC, and indicated that lncRNA CASC2 may present as a potential therapeutic target for the treatment of GC.