CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

Huo, Wenqian; Tan, Dan; Chen, Qing-Biao

doi:10.1159/000507828

Cited by 13 publications

(12 citation statements)

References 41 publications

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“…As the important components of the epigenetic regulatory complexes, CBX family proteins are involved in the development of multiple cancers, including UBC 6 , 7 , 26 , 27 . In this study, we found that CBX7 is the most remarkably downregulated gene among CBX family members in UBC tissues, as compared to normal tissues in TCGA dataset.…”

Section: Discussionmentioning

confidence: 99%

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10–ERK signaling

et al. 2021

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The chromobox (CBX) proteins mediate epigenetic gene silencing and have been implicated in the cancer development. By analyzing eight CBX family members in TCGA dataset, we found that chromobox 7 (CBX7) was the most strikingly downregulated CBX family member in urinary bladder cancer (UBC), as compared to normal tissues. Though dysregulation of CBX7 has been reported in multiple cancers, its specific role and clinical relevance in UBC remain unclear. Herein, we found that frequent downregulation of CBX7 in UBC specimens, which was due to its promoter hypermethylation, was correlated with poor prognosis. The ectopic expression of CBX7 suppressed UBC cell proliferation, migration, invasion, and cancer stemness, whereas CBX7 depletion promoted cancer cell aggressiveness. Importantly, CBX7 overexpression in UBC cells inhibited tumorigenicity, whereas CBX7 depletion promoted the tumor development, indicating its tumor-suppressive role in UBC. Using RNA-seq and chromosome immunoprecipitation (ChIP) assays, we identified aldo-keto reductase family 1 member 10 (AKR1B10) as a novel downstream target of CBX7, which was negatively modulated by CBX7 in a PRC1-dependent manner and involved in stimulating ERK signaling. Consistently, AKR1B10 overexpression induced cancer cell aggressiveness, whereas suppression of AKR1B10 by siRNA or its small molecular inhibitor, oleanolic acid, reversed the CBX7 deficiency-induced cellular effects. AKR1B10 overexpression was negatively associated with CBX7 downregulation and predicted poor clinical outcomes in UBC patients. Taken together, our results indicate that CBX7 functions as a tumor suppressor to downregulate AKR1B10 and further inactivates ERK signaling. This CBX7/AKR1B10/ERK signaling axis may provide a new therapeutic strategy against UBC.

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Section: Discussionmentioning

confidence: 99%

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10–ERK signaling

et al. 2021

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“…All these and previous findings on CASC9 suggested that CASC9 might be a novel marker for CRC prognosis. In fact, there are many reports that CASC9 is involved in non-small cell lung carcinoma, bladder cancer, thyroid cancer, hepatocellular carcinoma, nasopharyngeal cancer, and lung cancer ( Jin et al, 2019 ; Zeng et al, 2019 ; Chen Y. et al, 2020 ; Huo et al, 2020 ; Zhao et al, 2020 ). It has been suggested that CASC9 is a novel diagnostic, prognostic, and therapeutic target in cancer treatment ( Qian et al, 2020 ; Sharma et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have reported that CASC9 knockdown or silencing reduced cell proliferation, invasion, and migration ( Jin et al, 2019 ; Zhang et al, 2019 ; Chen Y. et al, 2020 ; Ding et al, 2020 ; Fang et al, 2020 ; Huo et al, 2020 ). We are the first to perform similar experiments in CRC cell lines.…”

Section: Discussionmentioning

confidence: 99%

Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial–Mesenchymal Transition Pathways

Khan

Law

2021

Front. Mol. Biosci.

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BackgroundColorectal cancer (CRC) is the third most common cancer worldwide. Many recent studies have demonstrated that different long non-coding RNAs (lncRNAs) are involved in the initiation, advancement, and metastasis of many cancers including CRC. Cancer susceptibility candidate 9 (CASC9) is an lncRNA that has been reported in many cancers, but its role in CRC is poorly understood. In this study, we aimed to examine the expression of CASC9 in CRC cell lines and to determine the mechanism of action of CASC9 in CRC carcinogenesis.MethodsThe expression of CASC9 in CRC tissues was compared with normal samples from publicly available datasets in The Cancer Genome Atlas (TCGA) and The Encyclopedia of RNA Interactomes (ENCORI). CASC9 expression was further verified in four CRC cell lines (DLD1, HT-29, SW480, and HCT-116) and normal colorectal cell line (CCD-112CoN) by real-time quantitative polymerase chain reaction (RT-qPCR). After gene silencing in HCT-116 and SW480, Cell Counting Kit-8 assay, clonogenic assay, and wound healing assay were performed to evaluate cell proliferation, viability, and migration index of cells. Western blotting was used to explore the key pathways involved.ResultsCASC9 was significantly upregulated as analyzed from both public datasets TCGA and ENCORI where its overexpression was associated with poor survival of CRC patients. Similarly, CASC9 was significantly overexpressed in the CRC cell lines compared with normal cells studied. The silencing of CASC9 in HCT-116 and SW480 attenuated cell proliferation and migration significantly. Furthermore, pathways investigations showed that silencing of CASC9 significantly induced autophagy, promoted AMP-activated protein kinase (AMPK) phosphorylation, inhibited mTOR and AKT signaling pathways, and altered epithelial–mesenchymal transition (EMT) marker protein expression.ConclusionWe demonstrated that silencing of CASC9 contributes to the reduced CRC cell proliferation and migration by regulating autophagy and AKT/mTOR/EMT signaling. Therefore, CASC9 plays an important role in carcinogenesis, and its expression may act as a prognostic biomarker and a potential therapeutic target of CRC management.

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“…lncRNA cancer susceptibility candidate 9 (CASC9) is an lncRNA situated at human 8q21.13 chromosome. Earlier studies have revealed its expression in cases with liver cancer and those with bladder cancer and its association with tumor prognosis [ 12 , 13 ]. Moreover, one recent study has found its expression in cases with colorectal cancer (CRC) [ 14 ], which suggests that lncRNA CASC9 is probably a potential biomarker of CRC.…”

Section: Introductionmentioning

confidence: 99%

Changes and Prognostic Value of lncRNA CASC9 in Patients with Advanced Colon Cancer after Chemotherapy

Jiao¹,

Liu²,

Zhao³

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. Colon cancer (CC) shows a gradual increasing incidence in recent years, and chemotherapy is a frequently adopted treatment for patients with middle or advanced colon cancer (ACC), but it lacks prognostic markers after CC. Methods. The changes of lncRNA CASC9 in 58 patients with CC were determined using a real-time quantitative PCR (qRT-PCR) assay before and after chemotherapy, and the correlation of serum lncRNA CASC9 with efficacy of FOLFOX4 regimen (oxaliplatin + calcium folinate + fluorouracil) was analyzed. The patients were followed up to understand the association of lncRNA CASC9 with overall survival (OS) and progression-free survival (PFS). Results. Patients with CC showed notably higher lncRNA CASC9 expression than controls, and lncRNA CASC9 presented an association with the clinical stage of the patients. In addition, lncRNA CASC9 demonstrated a clinical value in predicting efficacy on patients and acted as one independent prognostic factor for PFS in patients with ACC. Conclusions. With increased expression of serum lncRNA CASC9, patients with ACC suffered an unfavorable chemotherapy effect. In addition, serum lncRNA CASC9 is a promising sensitive indicator for prediction of ACC and is related to the clinical efficacy and prognosis of patients.

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CASC9 Facilitates Cell Proliferation in Bladder Cancer by Regulating CBX2 Expression

Cited by 13 publications

References 41 publications

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10–ERK signaling

CBX7 suppresses urinary bladder cancer progression via modulating AKR1B10–ERK signaling

Cancer Susceptibility Candidate 9 (CASC9) Promotes Colorectal Cancer Carcinogenesis via mTOR-Dependent Autophagy and Epithelial–Mesenchymal Transition Pathways

Changes and Prognostic Value of lncRNA CASC9 in Patients with Advanced Colon Cancer after Chemotherapy

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