Long Non-coding RNA TDRKH-AS1 Promotes Colorectal Cancer Cell Proliferation and Invasion Through the β-Catenin Activated Wnt Signaling Pathway

Yang, Jiao; Zhou, Jialiang; Jin, Yecheng; Yang, Yingxin; Song, Mingxu; Zhang, Ling; Zhou, Jiayan; Zhang, Jiwei

doi:10.3389/fonc.2020.00639

Cited by 14 publications

(11 citation statements)

References 38 publications

(41 reference statements)

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“…Active β-Catenin signaling depends on its nuclear translocation and is strongly linked with EMT processes and aerobic glycolysis in different cancers ( Cai et al, 2018 ; Fang et al, 2019 ; Zuo et al, 2020 ). In CRC, dysregulated β-Catenin signaling participates in the regulation of tumor invasion, metastasis formation and aerobic metabolism, and various mutations in crucial regulatory factors of the Wnt/β-Catenin pathway have already been widely noted in CRC ( Jiao et al, 2020 ; Wang et al, 2020 ; Xue et al, 2020 ; Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

Tian

Liu

et al. 2021

Front. Cell Dev. Biol.

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Previous studies reported that Follistatin-like 3 (FSTL3) is abundantly expressed in several solid tumors and participate in the regulation of cell metabolism. However, the clinico-pathological significance, biological role and molecular mechanism of FSTL3 in colorectal cancer (CRC) is still unclear. Here we report that the expression level of FSTL3 in colon cancer specimens was significantly higher, compared to normal tissue and interestingly, the expression of FSTL3 was related to lymph node metastasis, tumor stage, tumor size, and intravascular emboli (IVE). As an upstream molecular event, we found that transcriptional regulation of FSTL3 was highly dependent on YAP1 de-phosphorylation events and that increased FSTL3 expression readily activated the β-Catenin pathway, which is a well-known signaling hub that promotes EMT processes and aerobic glycolysis in cancer cells. We found that elevated FSTL3 expression strongly promotes migration, invasion and metastatic formation of CRC cells by directly activating β-Catenin -mediated EMT and aerobic glycolysis. In the xenograft mouse model, FSTL3 expression was linked to increased metastatic formation of CRC cells. Together, the activation of YAP1 induces FSTL3 expression. FSTL3-mediated β-Catenin pathway activation promotes EMT and aerobic glycolysis and therefore affecting the invasive and metastatic capacity of CRC cells. The abundant FSTL3 expression is a poor prognostic factor and pharmacological targeting of YAP1 can counteract FSTL3 expression, suggesting a promising therapeutic target for anti-metastatic strategies in patients suffering from CRC.

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Section: Discussionmentioning

confidence: 99%

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

Tian

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…Among the 12 PHRLs, AC011978.2, AC110995.1, YTHDF3-AS1, AL512380.1, HSD11B1-AS1, AL451085.3, and AL109955.1 have not been reported to date. TDRKH-AS1 was reported to promote colorectal cancer (CRC) progression through the Wnt/β-catenin signaling pathway ( Jiao et al, 2020 ). In addition, its differential expression with copy number alteration was positively associated with longer OS in lung adenocarcinoma ( Wang L. et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer

Zhang

Ding

et al. 2021

Front. Cell Dev. Biol.

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Background: Female breast cancer is currently the most frequently diagnosed cancer in the world. This study aimed to develop and validate a novel hypoxia-related long noncoding RNA (HRL) prognostic model for predicting the overall survival (OS) of patients with breast cancer.Methods: The gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 200 hypoxia-related mRNAs were obtained from the Molecular Signatures Database. The co-expression analysis between differentially expressed hypoxia-related mRNAs and lncRNAs based on Spearman’s rank correlation was performed to screen out 166 HRLs. Based on univariate Cox regression and least absolute shrinkage and selection operator Cox regression analysis in the training set, we filtered out 12 optimal prognostic hypoxia-related lncRNAs (PHRLs) to develop a prognostic model. Kaplan–Meier survival analysis, receiver operating characteristic curves, area under the curve, and univariate and multivariate Cox regression analyses were used to test the predictive ability of the risk model in the training, testing, and total sets.Results: A 12-HRL prognostic model was developed to predict the survival outcome of patients with breast cancer. Patients in the high-risk group had significantly shorter median OS, DFS (disease-free survival), and predicted lower chemosensitivity (paclitaxel, docetaxel) compared with those in the low-risk group. Also, the risk score based on the expression of the 12 HRLs acted as an independent prognostic factor. The immune cell infiltration analysis revealed that the immune scores of patients in the high-risk group were lower than those of the patients in the low-risk group. RT-qPCR assays were conducted to verify the expression of the 12 PHRLs in breast cancer tissues and cell lines.Conclusion: Our study uncovered dozens of potential prognostic biomarkers and therapeutic targets related to the hypoxia signaling pathway in breast cancer.

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“…MIR200CHG can stimulate proliferation, invasion, and drug resistance in breast cancer by interacting with and normalizing YB-1, which is involved in regulating hypoxia-dependent gene transcription, and the hypo-phosphorylation of lactate metabolism related-signaling such as mTOR and HIF1 in cancer ( 56 – 58 ). Up-regulation of TDRKH-AS1 is strongly associated with malignant features of colorectal cancer as well as their unfavorable prognoses ( 59 , 60 ), and TMPO-AS1 silencing reduced cancer cells proliferation and stemness while promoting apoptosis in CRC cells ( 61 ). Oncogenic TMPO-AS1 was also abnormally up-regulated in retinoblastoma tissues which served as ceRNA to modulate the expression of HIF-1α, a core hub regulating cellular lactate metabolism by sponging miR199a-5p ( 62 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

et al. 2022

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BackgroundLung cancer has been a prominent research focus in recent years due to its role in cancer-related fatalities globally, with lung adenocarcinoma (LUAD) being the most prevalent histological form. Nonetheless, no signature of lactate metabolism-related long non-coding RNAs (LMR-lncRNAs) has been developed for patients with LUAD. Accordingly, we aimed to develop a unique LMR-lncRNA signature to determine the prognosis of patients with LUAD.MethodThe Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to derive the lncRNA expression patterns. Identification of LMR-lncRNAs was accomplished by analyzing the co-expression patterns between lncRNAs and LMR genes. Subsequently, the association between lncRNA levels and survival outcomes was determined to develop an effective signature. In the TCGA cohort, Cox regression was enlisted to build an innovative signature consisting of three LMR-lncRNAs, which was validated in the GEO validation cohort. GSEA and immune infiltration analysis were conducted to investigate the functional annotation of the signature and the function of each type of immune cell.ResultsFourteen differentially expressed LMR-lncRNAs were strongly correlated with the prognosis of patients with LUAD and collectively formed a new LMR-lncRNA signature. The patients could be categorized into two cohorts based on their LMR-lncRNA signatures: a low-risk and high-risk group. The overall survival of patients with LUAD in the high-risk group was considerably lower than those in the low-risk group. Using Cox regression, this signature was shown to have substantial potential as an independent prognostic factor, which was further confirmed in the GEO cohort. Moreover, the signature could anticipate survival across different groups based on stage, age, and gender, among other variables. This signature also correlated with immune cell infiltration (including B cells, neutrophils, CD4+ T cells, CD8+ T cells, etc.) as well as the immune checkpoint blockade target CTLA-4.ConclusionWe developed and verified a new LMR-lncRNA signature useful for anticipating the survival of patients with LUAD. This signature could give potentially critical insight for immunotherapy interventions in patients with LUAD.

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Long Non-coding RNA TDRKH-AS1 Promotes Colorectal Cancer Cell Proliferation and Invasion Through the β-Catenin Activated Wnt Signaling Pathway

Cited by 14 publications

References 38 publications

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

Development and Validation of a Novel Hypoxia-Related Long Noncoding RNA Model With Regard to Prognosis and Immune Features in Breast Cancer

Development and Validation of Lactate Metabolism-Related lncRNA Signature as a Prognostic Model for Lung Adenocarcinoma

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