[Corrigendum] Long non­coding RNA CASC11 interacts with YBX1 to promote prostate cancer progression by suppressing the p53 pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, concerning the Transwell assay experiments shown in Fig. 3G and I on p. 8, the data panel showing the result of the 'LNCaP / sh­CASCS11­1' experiment in Fig. 3G appeared to be overlapping with the 'LNCaP / Vector' experiment in Fig. 3I, even though the data were intended to have shown the results from differently performed experiments. After having re­examined their original data, the authors have realized that Fig. 3G and I were inadvertently assembled incorrectly. The revised version of Fig. 3, showing the correct data for the 'LNCaP / Vector' experiment in Fig. 3I, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors thank the interested reader for drawing this matter to their attention, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 110, 2022; DOI: 10.3892/ijo.2022.5400].

Expression of selected long non-coding RNAs in gastric cancer cells treated with coumarin: Possible mechanisms for anti-cancer activity.

Long non-coding RNAs (lncRNAs) can be utilized as prognostic indicators of gastric cancer since they can affect several cancer-related processes. Coumarin is a natural product with some useful anti-cancer properties. Here, we measured the expression of selected lncRNAs (RuPAR, SNHG6, CASC11, and their targets, miR-340-5p, p21, E-cadherin, and CDK1) in AGS gastric cancer cells treated with coumarin. MTT test has been utilized for assessing the AGS cells' cell viability after exposure to coumarin. The expression of the lncRNAs (RuPAR, SNHG6, and CASC11) and miR-340-5p was evaluated via qRT-PCR. Western blot analysis has been utilized to determine changes in p21, E-cadherin, and CDK1 expression. Coumarin decreased AGS viability in a dose-dependent manner. The coumarin treated cells had lower levels of the mRNAs known to be targets of lncRNAs SNHG6 and CASC11 compared to control. Additionally, the coumarin group had increased levels of lncRNA RuPAR expression when compared with the control group. Some lncRNA targets, including p21, E-cadherin, and CDK1, showed lower expression in the coumarin group compared to the control by Western blotting. Coumarin could be a promising pharmacological candidate to be included in gastric cancer treatment regimens because it modulates lncRNAs and their targets.

Lncrna CASC11 aggravates diabetic nephropathy via targeting FoxO1.

Background: To explore the biological effects of CASC11 on aggravating diabetic nephropathy (DN) by regulating FoxO1 (forkhead transcription factor O1). Methods: Serum levels of CASC11 and FoxO1 in DN patients were detected. The possibility of CASC11 in predicting the onset of DN was analyzed by depicting ROC curves. Correlation between CASC11 and FoxO1 was evaluated by Pearson correlation test. After intervening CASC11 and FoxO1 levels, we found that changes in proliferative and migratory abilities in high glucose (HG)induced kidney mesangial cells were determined respectively. Protein levels of TGF-ß1 and Smads regulated by both CASC11 and FoxO1 were examined by Western blot.

A review on the role of CASC11 in cancers.

The long non-coding RNA (lncRNA) cancer susceptibility 11 (CASC11) is a newly identified lncRNA located on chromosome 8q24.21. The expression of lncRNA CASC11 has been found to be elevated in different cancer types and the prognosis of the tumor is inversely correlated with the high CASC11 expression. Moreover, lncRNA CASC11 has an oncogenic function in cancers. The biological characteristics of the tumors, such as proliferation, migration, invasion, autophagy, and apoptosis can be controlled by this lncRNA. In addition to interacting with miRNAs, proteins, transcription factors, and other molecules, the lncRNA CASC11 modulates signaling pathways including Wnt/ß-catenin and epithelial-mesenchymal transition. In this review, we have summarized studies on the role of lncRNA CASC11 in the carcinogenesis from cell lines, in vivo, and clinical perspectives.

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.

Correlation between plasma lncRNA CASC11 and malignancy in lung adenocarcinoma patients and the prognostic value of lncRNA CASC11.

Objective: To study the connection between lncRNA CASC11 plasma expression and clinical characteristics as well as prognoses of patients. Methods: Sixty lung adenocarcinoma (LUAD) patients and 60 healthy adults participated in this research. LncRNA CASC11 expression was detected by quantitative real-time PCR and the relationships between lncRNA CASC11 plasma expression and patient prognosis and clinical characteristics were analyzed. Results: LncRNA CASC11 was highly expressed in LUAD tissues and plasma (p < 0.05). Receiver operating characteristic curve analysis indicated the diagnostic value of lncRNA CASC11 in LUAD (p < 0.0001). Higher plasma lncRNA CASC11 expression indicated worse patient prognoses (p < 0.05). Plasma lncRNA CASC11 level was also closely related to tumor differentiation and tumor-node-metastasis stage (p < 0.05). Conclusion: Plasma lncRNA CASC11 may be a potential biomarker for LUAD diagnosis and prognosis.

CASC11 and PVT1 spliced transcripts play an oncogenic role in colorectal carcinogenesis.

Cancer is fundamentally a genetic disorder that alters cellular information flow toward aberrant growth. The coding part accounts for less than 2% of the human genome, and it has become apparent that aberrations within the noncoding genome drive important cancer phenotypes. The numerous carcinogenesis-related genomic variations in the 8q24 region include single nucleotide variations (SNVs), copy number variations (CNVs), and viral integrations occur in the neighboring areas of the MYC locus. It seems that MYC is not the only target of these alterations. The MYC-proximal mutations may act via regulatory noncoding RNAs (ncRNAs). In this study, gene expression analyses indicated that the expression of some PVT1 spliced linear transcripts, CircPVT1, CASC11, and MYC is increased in colorectal cancer (CRC). Moreover, the expression of these genes is associated with some clinicopathological characteristics of CRC. Also, in vitro studies in CRC cell lines demonstrated that CASC11 is mostly detected in the nucleus, and different transcripts of PVT1 have different preferences for nuclear and cytoplasmic parts. Furthermore, perturbation of PVT1 expression and concomitant perturbation in PVT1 and CASC11 expression caused MYC overexpression. It seems that transcription of MYC is under regulatory control at the transcriptional level, i.e., initiation and elongation of transcription by its neighboring genes. Altogether, the current data provide evidence for the notion that these noncoding transcripts can significantly participate in the MYC regulation network and in the carcinogenesis of colorectal cells.

In Vivo Genome-Wide CRISPR Activation Screening Identifies Functionally Important Long Noncoding RNAs in Hepatocellular Carcinoma.

BACKGROUND & AIMS: Long noncoding RNAs (lncRNAs) are found to have profound impacts on diverse cellular processes. Although high-throughput sequencing studies have shown the differential lncRNA expression profiles between hepatocellular carcinoma (HCC) and nontumor livers, the functional impacts of lncRNAs on HCC development await further investigation. Herein, we sought to address the functional roles of lncRNAs in HCC pathogenesis by in vivo functional screening. METHODS: We performed genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/dead CRISPR-associated protein 9 (dCas9) lncRNA activation screening in HCC xenografts. We characterized the clinical relevance of positively selected lncRNAs using transcriptomic data sets. We used CRISPR-based gene activation and knockdown approaches to show the functional roles of positively selected lncRNAs including Cancer Susceptibility 11 (CASC11) in HCC. RNA sequencing and chromatin isolation by RNA purification sequencing were used to investigate the molecular mechanisms of CASC11 in HCC progression. RESULTS: The in vivo functional screening identified 1603 positively selected lncRNAs, 538 of which were overexpressed in HCC patients. Systematic transcriptomic data analysis and clinical investigation showed that patients with high expression of these lncRNA candidates correlated with aggressive tumor behaviors. Overexpression of these lncRNAs aggravated HCC cell growth. Detailed characterization of a lncRNA candidate, CASC11, showed its pivotal role in cell proliferation and tumor growth. Mechanistically, chromatin isolation by RNA purification sequencing showed that CASC11 was bound to the CASC11/MYC proto-oncogene shared promoter region on chromosome 8q24. CASC11 modulated the transcriptional activity of MYC in a cis-regulatory manner, which affected the expression of MYC downstream target genes, consequently promoting G1/S progression. CONCLUSIONS: Our study showed the power of in vivo CRISPR screening, which comprehensively investigated the functionality of lncRNAs in HCC progression, providing a rationale for targeting these lncRNAs clinically.

Long non­coding 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 cancer­related death worldwide. The roles and mechanisms of long non­coding 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 loss­of­function assays were utilized to explore the biological role of CASC11 in PCa initiation and progression. RNA­sequencing, RNA pull­down 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 CASC11­silenced PCa cells, whereas the opposite effects were detected in CASC11­overexpressing cells. Mechanistically, CASC11 promoted progression of the cell cycle and competitively interacted with Y­box binding protein 1 (YBX1) to block the p53 pathway. Given this, poly (ß­amino ester) (PBAE)/small interfering RNA­CASC11 (si­CASC11) nanoparticles were applied to inhibit CASC11 expression and enhance the antitumor effect in vivo. The results revealed that PBAE/si­CASC11 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 lncRNA­directed therapeutic strategy particularly for the treatment of patients with PCa.

Critical roles of the lncRNA CASC11 in tumor progression and cancer metastasis: The biomarker and therapeutic target potential.

The frequency of human suffering from cancer is increasing annually across the globe. This has fueled numerous investigations aimed at the prevention and cure of various cancers. Long non-coding RNA (lncRNA) are known to play a crucial role in cancer. For instance, cancer susceptibility candidate 11 (CASC11), as one of the long non-coding RNAs, has been reported to be overexpressed in various tumors. This review elucidates the mechanism by which lncRNA CASC11 regulates tumors' biological processes and affirms its value as a therapeutic target for tumors. Through systematic analysis and review of relevant articles in PubMed, we revealed the pathophysiological mechanism of CASC11 on the tumor by regulating the biological processes of tumor such as proliferation, autophagy, apoptosis, thereby promoting tumor metastasis. We also revealed the regulatory pathways of CASC11 in different tumors, for instance by acting on a variety of microRNAs, oncogenic proteins, carcinogens, and transcription factors. Consequently, CASC11 regulates cancer proliferation, apoptosis, and invasion by altering the WNT/ß-catenin signaling pathway and epithelial-mesenchymal transition (EMT). Furthermore, CASC11 expression has a high pertinence with clinical prognosis, suggesting that it is a potential marker for malignant tumors or a clinical adjuvant therapy in the future.

[Role of LncRNA CASC11 in the malignant transformation of 16HBE cells induced by glycidyl methacrylate].

OBJECTIVE: To investigate the effect of trending up-regulation LncRNA CASC11 which is differentially expressed during the malignant transformation of human bronchial epithelial cells(16 HBE) induced by glycidyl methacrylate(GMA). METHODS: After 16 HBE cells were repeatedly exposed to low concentration GMA(8 µg/mL), the 10 th, 20 th and 30 th passage cells of the GMA group and the DMSO solvent control group were collected. High throughput LncRNA microarray were used to screen the differentially expressed LncRNAs at different stages. Short Time-series Expression Miner and bioinformatics tool RPISeq were used to screen and predict the potential targets of specific LncRNA. Real-time fluorescent quantitative PCR(qPCR) and Western blot were used to detect the relative expression of specific LncRNA and the content of its target protein respectively. RESULTS: The specific differential expression of LncRNA CASC11 in the process of GMA-induced malignant transformation of 16 HBE cells showed a trend of up-regulation. Compared with the control cells in the same period, the P10, P20 and P30 generation cells were down-regulated by 1.64 times, up-regulated by 2.01 times, and up-regulated by 2.66 times, respectively. Western blot showed that the levels of cyclin-dependent kinase 1(CDK1), cyclinB1 and cyclinB2 in P10, P20 and P30 cells after exposure were lower than those in DMSO control group during the same period, which was consistent with the microarray results. CONCLUSION: The differential expression of LncRNA CASC11 in the process of GMA-induced 16 HBE cell malignant transformation was up-regulated trendingly. It is speculated that it may block or delay cell cycle progression by inhibiting CDK1.

A crucial role for the long non-coding RNA CASC11 in the pathogenesis of human cancers.

Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides in length. Although they do not encode proteins, lncRNAs can regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging data show that lncRNAs are important for tumorigenesis and cancer progression. Cancer susceptibility candidate 11 (CASC11) is a prominent lncRNA that is upregulated in various types of cancers. Moreover, its overexpression correlates with larger tumor size, more advanced cancer stages, cancer metastasis, and poor overall survival for most types of cancer. Functionally, the knockdown of CASC11 can inhibit cell proliferation, invasion, and migration, while enhancing apoptosis through its regulation of gene expression and signaling pathways and its interactions with functional proteins. Here, we discuss the identification, expression, and function of CASC11. Additionally, we discuss the potential roles of CASC11 as a diagnostic biomarker, prognostic biomarker, and therapeutic target in various cancers.

The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2.

BACKGROUND: We previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2. METHODS: We identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression. RESULTS: We found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis. CONCLUSION: Our study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.

Long noncoding RNA CASC11 promotes hepatocarcinogenesis and HCC progression through EIF4A3-mediated E2F1 activation.

BACKGROUND: Growing evidences have been revealing that long noncoding RNAs are vital factors in oncogenesis and tumor development. Among them, cancer susceptibility candidate 11 (CASC11) has displayed an impressively essential role in various kinds of cancers including hepatocellular carcinoma (HCC). Nevertheless, its role and potential mechanism in HCC still remain to be fully investigated. METHODS: CASC11 expression level was evaluated by real-time polymerase chain reaction, western blotting, and in situ hybridization staining in HCC patients, and its prognostic effect was analyzed. The role of CASC11 in HCC tumorigenesis and progression was investigated by cell proliferation assay, transwell assay, extracellular acidification rate, western blotting, flow cytometry, and an in vivo xenograft model. The interactions among CASC11, E2F transcription factor 1 (E2F1), and eukaryotic translation initiation factor 4A3 (EIF4A3) were explored by using quantitative reverse transcriptase polymerase chain reaction, western blotting, RNA-binding protein immunoprecipitation assay, and chromatin immunoprecipitation assays. RESULTS: Upregulation of CASC11 was confirmed in HCC tissues and associated with poor prognosis. Loss of function assays showed inhibition of CASC11 expression suppressed HCC cells proliferation, mobility, and glucose metabolism and promoted apoptosis. E2F1 expression significantly decreased after inhibition of CASC11. Rescue experiments illustrated that E2F1 overexpression alleviated the suppression of CASC11 inhibition on HCC progression in vitro and in vivo. Mechanistically, CASC11 recruited EIF4A3 to enhance the stability of E2F1 mRNA. CASC11 and E2F1 impacted the activation of the NF-κB signaling and PI3K/AKT/mTOR pathway and further regulated the expression PD-L1 that is an important target of immunotherapy. In addition, we identified YY1 could modulate CASC11 expression by binding to its promoter. CONCLUSIONS: Our data revealed that CASC11 promoted the progression of HCC by means of EIF4A3-mediated E2F1 upregulation, indicating CASC11 is a promising diagnostic biomarker and therapeutic target for HCC.

CASC11 Overexpression Predicts Poor Prognosis and Regulates Cell Proliferation and Apoptosis in Ovarian Carcinoma.

INTRODUCTION: It is known that CASC11 can promote colorectal cancer. However, the function of CASC11 in ovarian carcinoma (OC) remains elusive. METHODS: In this study, we measured the expression levels of CASC11 and miR-182 in both OC and healthy control samples by performing qPCR. The interaction between CASC11 and miR-182 was analyzed by the overexpression experiment and qPCR. Cell apoptosis was analyzed by cell apoptosis assay, and the prognostic value of CASC11 for OC was analyzed by survival curve analysis. RESULTS: We found that CASC11 and microRNA-182 (miRNA-182) were upregulated in OC. Plasma CASC11 was upregulated in OC patients and predicted early-stage OC. Follow-up study revealed that high plasma levels of CASC11 were closely correlated with poor survival conditions of OC patients. CASC11 and miRNA-182 were positively correlated in OC. Overexpression of CASC11 mediated the upregulation of miRNA-182 in cells of OC cell lines, while miRNA-182 overexpression did not significantly affect CASC11 expression. Overexpression of CASC11 and miRNA-182 promoted cancer cell proliferation and inhibited cancer cell apoptosis. CONCLUSION: Therefore, CASC11 overexpression predicts poor prognosis and CASC11 regulates cell proliferation and apoptosis as well as microRNA-182 expression in ovarian carcinoma.

LncRNA CASC11 is upregulated in postmenopausal osteoporosis and is correlated with TNF-α.

PURPOSE: In this study, we aimed to investigate the role of lncRNA cancer susceptibility 11 (CASC11) and tumor necrosis factor (TNF-α) in postmenopausal osteoporosis (POP). METHODS AND MATERIALS: POP patients and healthy controls were included in this study and levels of CASC11 and TNF-α in plasma of those participants were measured by qPCR and Western blot, respectively. ROC curve was used for diagnostic analysis. Patients were followed up for 2 years and the correlations between the levels of CASC11 and TNF-α and disease conditions were analyzed. RESULTS: We found that CASC11 and TNF-α were both upregulated in plasma of POP patients than in healthy controls. Plasma levels of CASC11 and TNF-α were positively correlated in both POP patients and in healthy controls. Upregulation of CASC11 and TNF-α distinguished POP patients from healthy controls. Treatment and follow-up study showed that high CASC11 levels were significantly correlated with prolonged treatment course and high recurrence rate. Plasma levels of CASC11 and TNF-α decreased after treatment. CASC11 overexpression led to upregulated TNF-α in osteoclasts. CONCLUSION: CASC11 is upregulated in POP and is correlated with TNF-α.

LncRNA LINC01116 Promotes Cancer Cell Proliferation, Migration And Invasion In Gastric Cancer By Positively Interacting With lncRNA CASC11.

PURPOSE: The oncogenic roles of lncRNA LINC01116 have been reported in several types of cancer, while its involvement in gastric cancer is unknown. This study aimed to investigate the involvement of LINC01116 in gastric cancer. METHODS: Gene expression was detected by qPCR. Correlations were analyzed by linear regression. Overexpression and siRNA silencing techniques were used to analyze gene functions. Cell invasion and migration were analyzed by Transwell assays. RESULTS: LINC01116 and lncRNA CASC11 were both upregulated in cancer tissues compared to cancer-adjacent tissues. Expression levels of LINC01116 and CASC11 were increased with the increase in clinical stages. Expression levels of LINC01116 and CASC11 were positively correlated. Overexpression of LINC01116 mediated the upregulated CASC11 in gastric cancer cells, and CASC11 overexpression also led to overexpressed LINC01116. Overexpression of LINC01116 and CASC11 led to promoted invasion and migration of gastric cancer cells. Rescue experiments showed that CASC11 knockdown attenuated the effects of LINC01116 overexpression. Overexpression of LINC01116 failed to significantly affect cancer cell proliferation. CONCLUSION: LINC01116 promoted cancer cell invasion and migration in gastric cancer by positively interacting with CASC11.

The positive feedback loop FOXO3/CASC11/miR-498 promotes the tumorigenesis of non-small cell lung cancer.

An increasing number of studies have indicated that long noncoding RNAs (lncRNAs) are involved in the regulation of non-small-cell lung cancer (NSCLC). Nevertheless, there are still numerous undiscovered mechanisms underlying this molecular regulation. Here, the results illustrated that CASC11 is overexpressed in NSCLC tumor tissues and cell lines, which is closely related to the clinical features of NSCLC and poor survival. In functional experiments, CASC11 was shown to promote proliferation and cycle progression and enhance NSCLC tumorigenesis. In mechanical investigations, CASC11 was shown to target the miR-498/FOXO3 axis via a canonical competing endogenous RNA (ceRNA). In return, the transcription factor FOXO3 targets the CASC11 promoter region, thereby accelerating its transcription. Our findings demonstrate a crucial role for CASC11 as an oncogene in promoting NSCLC. These results reveal that CASC11 might be a potential therapeutic target for NSCLC.

LncRNA CASC11 promotes the cervical cancer progression by activating Wnt/beta-catenin signaling pathway.

BACKGROUND: Studies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression. MATERIALS: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/ß-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation. RESULTS: We discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/ß-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo. CONCLUSION: Our study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/ß-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.