Long noncoding RNA cancer susceptibility candidate�9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2

Jiang, Baohong; Li, Yuehua; Qu, Xiaofei; Zhu, Hongbo; Tan, Ye; Fan, Q.; Jiang, Yiling; Liao, Mingchu; Wu, Xiaoping

doi:10.3892/ijmm.2018.3812

Cited by 22 publications

(16 citation statements)

References 33 publications

(26 reference statements)

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“…In addition, CASC9 promoted cell growth and decreased apoptosis in vitro and was required for tumor formation in nude mice in vivo . These data provide strong evidence supporting an oncogenic role of CASC9 in CRC, in accordance with previous reports of CASC9 functioning as an oncogene in several other cancers, including hepatocellular carcinoma, esophageal squamous cell carcinoma, gastric cancer, ovarian cancer, glioma, and breast cancer [33–39]. These results demonstrate that higher levels of CASC9 are related to more aggressive disease.…”

Section: Discussionsupporting

confidence: 92%

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

Luo

Geng

Zhang

et al. 2019

J Exp Clin Cancer Res

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Background Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related death worldwide. Increasing evidence indicates that the deregulation of long noncoding RNAs (lncRNAs) contributes to tumor initiation and progression; however, little is known about the biological role of cancer susceptibility candidate 9 (CASC9) in CRC. Methods Novel lncRNAs potentially involved in CRC tumorigenesis were identified from datasets downloaded from The Cancer LncRNome Atlas and The Atlas of Noncoding RNAs in Cancer. The CRC cell lines HCT-116, HCT-116 p53 −/− , SW620, SW480, HT-29, LoVo, LS-174T, and RKO were used. Colony-formation, MTS, cell-cycle, apoptosis, and in-vivo tumorigenesis assays were used to determine the role of CASC9 in CRC cell growth in vitro and in vivo. Potential interaction between CASC9 and cleavage and polyadenylation specificity factor subunit 3 (CPSF3) was evaluated using RNA immunoprecipitation and RNA-protein pull-down assays. RNA-sequencing was performed to analyze gene expression following CASC9 knockdown. RT-qPCR, western blotting, and mRNA decay assays were performed to study the mechanisms involved. Results CASC9 was frequently upregulated in CRC, which was correlated with advanced TNM stage, and higher CASC9 levels were associated with poor patient outcomes. Knockdown of CASC9 inhibited growth and promoted apoptosis in CRC cells, whereas ectopic CASC9 expression promoted cell growth in vitro and in vivo. We demonstrated that CPSF3 is a CASC9-interacting protein, and knockdown of CPSF3 mimicked the effects of CASC9 knockdown in CRC cells. Furthermore, we found that CASC9 exerts its oncogenic activity by modulating TGFβ2 mRNA stability and upregulating the levels of TGFβ2 and TERT, resulting in an increase in phosphorylated SMAD3 and activation of TGF-β signaling, and enhanced TERT complex function in CRC cells. Finally, CPSF3 was significantly upregulated in CRC tissues as compared with adjacent or non-adjacent normal colon tissues, and CASC9, CPSF3, and TGFβ2 levels in human CRC tissues were positively correlated. Conclusions CASC9 is a promising prognostic predictor for patients with CRC and the CASC9-CPSF3-TGFβ2 axis is a potential therapeutic target for CRC treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1263-3) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

Luo

Geng

Zhang

et al. 2019

J Exp Clin Cancer Res

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“…Therefore, it was hypothesized that CASC9 modulates the expression of HNF4G or interacts with it to affect the occurrence and progression of LUSC. Additionally, CASC9 has been reported to enhance the malignant potential of human cancer types, including breast cancer, hepatocellular carcinoma and ESCC, by interacting with numerous target genes, such as EZH2, heterogeneous nuclear ribonucleoprotein L and laminin subunit γ-2 (44)(45)(46). Although these target genes were not revealed in the bioinformatics analysis of the present study, the association between them and CASC9 in LUSC is also worth exploring in future studies.…”

Section: Discussionmentioning

confidence: 73%

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

Guo

Zeng

et al. 2019

Int J Oncol

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The cancer susceptibility candidate 9 (CASC9) gene has been reported to exert an oncogenic effect in several types of cancer. However, its role in lung squamous cell carcinoma (LUSC) is unknown. Therefore, the present study examined the expression of CASC9 in LUSC and non-cancer tissues by reverse transcription-quantitative polymerase chain reaction assays and by data mining of high-throughput public databases, including The Cancer Genome Atlas, the Gene Expression Omnibus, ArrayExpress and the Cancer Cell Line Encyclopedia. In vitro experiments were conducted to investigate the effects of CASC9 on the viability and the proliferation of LUSC cells. Furthermore, consulting the alteration status of CASC9 in LUSC from cBioPortal, functional enrichment analysis of co-expressed genes, prediction of potential transcription factors, and inspection of adjacent protein-coding genes were conducted to explore the potential molecular mechanism of CASC9 in LUSC. The results revealed that CASC9 was overexpressed in LUSC tissue, and significantly associated with the malignant progression of LUSC. In vitro experiments demonstrated that CASC9 knockdown by RNA interference attenuated the viability and proliferation of LUSC cells. Multiple copies of CASC9 gene were detected in 4 of 179 available sequenced LUSC cases. A functional enrichment analysis of 200 co-expressed genes indicated that these genes were significantly associated with terms, including 'cell-cell junction organization', 'desmosome organization', 'epidermis development', 'Hippo signaling pathway', 'pathogenic Escherichia coli infection' and 'PID HIF1 TF pathway'. Three genes, Fos-related antigen 2 (FOSL2), SWI/SNF complex subunit SMARCC2, and transcription factor COE1 (EBF1), were predicted by lncRNAMap to be associated with CASC9. Among these, the expression of FOSL2 and EBF1 was positively and negatively correlated with the expression of CASC9, respectively. Two adjacent protein-coding genes, cysteine-rich secretory protein LCCL domain-containing 1 and hepatocyte nuclear factor 4-γ, were also positively correlated with CASC9 expression. In conclusion, the present data suggest that CASC9 serves as an oncogene in LUSC and may be a promising target for alternative therapeutic options for patients with this condition.

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“…For example, increased lncRNA EBIC expression in ovarian cancer can improve cisplatin resistance though regulating the Wnt/β-catenin signaling pathway [28]. lncRNA/CASC9 regulates the MDR1 gene by binding to EZH2 and promoting doxorubicin-resistance in breast cancer [29]. In our study, we explored the relationships between MDR and expression of RP11-296E3.2 and LEF1-AS1 in 20 patients using an ATP-based tumor chemosensitivity assay (ATP-TCA).…”

Section: Discussionmentioning

confidence: 99%

Two Novel Long Noncoding RNAs – RP11-296E3.2 and LEF1-AS1can – Separately Serve as Diagnostic and Prognostic Bio-Markers of Metastasis in Colorectal Cancer

Shi

Zhang

et al. 2019

Med Sci Monit

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BackgroundLate diagnosis and metastasis are leading causes of the high mortality of colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) have been reported to play a critical role in the development and progression of CRC. This study aimed to explore the clinical significance of 2 novel lncRNAs – RP11-296E3.2 and LEF1-AS1 – including their expression pattern, as well as diagnostic and prognostic values, for metastatic CRC patients.Material/MethodslncRNAs expression was examined in tissues (91 cases) and plasma (60 cases) from CRC patients by real-time quantitative PCR (qRT-PCR), and the correlations between its expression and clinicopathological features and diagnosis values in metastasis were analyzed. TCGA datasets were further used to analyze their utility in prediction of overall survival (OS) and disease-free survival (DFS). ATP-based tumor chemosensitivity assay (ATP-TCA) was used to evaluated tumor chemoresistance.ResultsCompared with adjacent normal tissues, RP11-296E3.2 was significantly downregulated while LEF1-AS1 was significantly upregulated in cancer tissues (p=0.0143, p=0.0322, respectively). High levels of RP11-296E3.2 and LEF1-AS1 in tissues and plasma were correlated with tumor metastasis (p=0.0488, p=0.0252 in tissues, p=0.0331, p=0.1862 in plasma, respectively). Further analysis showed that RP11-296E3.2 sensitivity and specificity in diagnosis of CRC metastasis is better than CEA in plasma (0.690 and 0.621, and 0.621 and 0.500, respectively), and the OS of metastatic CRC patients with higher LEF1-AS1 expression levels in tissues was short (log-rank p<0.05).ConclusionsOur findings suggest that RP11-296E3.2 and LEF1-AS1 could separately serve as potential novel diagnosis and prognostic markers for CRC metastasis.

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Long noncoding RNA cancer susceptibility candidate�9 promotes doxorubicin‑resistant breast cancer by binding to enhancer of zeste homolog 2

Cited by 22 publications

References 33 publications

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer

The expression, significance and function of cancer susceptibility candidate�9 in lung squamous cell carcinoma: A bioinformatics and in�vitro investigation

Two Novel Long Noncoding RNAs – RP11-296E3.2 and LEF1-AS1can – Separately Serve as Diagnostic and Prognostic Bio-Markers of Metastasis in Colorectal Cancer

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