HCP5 is a SMAD3-responsive long non-coding RNA that promotes lung adenocarcinoma metastasis via miR-203/SNAI axis

Jiang, Lin; Wang, Ranran; Li, Fang; Ge, Xiaolu; Chen, Lingna; Zhou, Ming; Zhou, Yanhong; Wang, Xiong; Hu, Yerong; Tang, Xianming; Li, Guiyuan; Zheng, Li

doi:10.7150/thno.31097

Cited by 94 publications

(93 citation statements)

References 49 publications

(49 reference statements)

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“…Furthermore, miR-203 has been proven to be involved in the expression of several cancerrelated factors. MiR-203 suppressed ovarian carcinoma progression by inhibiting Survivin expression [25] and inhibited epithelial-mesenchymal transition by decreasing Snail and Slug expression, which are regarded as biomarkers of the epithelial-mesenchymal transition process [27]. This evidence suggests that miR-203 could potentially become a cancer therapeutic target and prognostic biomarker.…”

Section: Discussionmentioning

confidence: 92%

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

Chen

Yuan

et al. 2020

Pathobiology

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Objective: has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. Methods: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3′UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. Results: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. Conclusion: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

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Section: Discussionmentioning

confidence: 92%

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

Chen

Yuan

et al. 2020

Pathobiology

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“…[11][12][13] Some lncRNAs, such as HCP5, CAR10, NEAT1 and MALAT1, promote lung cancer metastasis via various mechanisms. 7,14,15 These findings suggest that the tumor metastasis-associated lncRNAs in lung cancer have potential prognostic implications. In the present study, we hypothesized that there were metastasis-associated lncRNAs in LUAD which were differentially expressed between metastatic and nonmetastatic primary cancer tissues, and the dysregulated lncRNA expression regulated the aggressiveness, or in general, the prognosis.…”

Section: Introductionmentioning

confidence: 83%

“…Several recent studies have focused on the involvement of lncRNAs in tumor metastasis because these lncRNAs have shown great promise in the discovery of new biomarkers for predicting prognosis in individual patients . Some lncRNAs, such as HCP5, CAR10, NEAT1 and MALAT1, promote lung cancer metastasis via various mechanisms . These findings suggest that the tumor metastasis‐associated lncRNAs in lung cancer have potential prognostic implications.…”

Section: Introductionmentioning

confidence: 99%

Unique metastasis‐associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma

Zhang

Han

et al. 2020

Thoracic Cancer

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Background Local relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis‐associated lncRNAs in patients with lung adenocarcinoma (LUAD). Methods Firstly, the potential metastasis‐associated lncRNAs were identified by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan‐Meier survival analysis, time‐dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis‐associated function of these six lncRNAs was confirmed by lncRNA over‐expression or depletion and in vitro transwell assays in LUAD cells. Results An lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649‐AS1, HNF4A‐AS1, FAM222A‐AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse‐free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility. Conclusions This novel six‐lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients. Key points Significant findings of the studyThe unique metastasis‐associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study addsThis signature had considerable prognostic value for prediction of relapse in LUAD patients.

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“…MiR‐203 expression was down‐regulated in NSCLC and negatively correlated with clinical tumour‐node‐metastasis (TNM) stages . Jiang et al demonstrated that HCP5 repressed miR‐203 acting as a molecular sponge, stabilized Snail and Slug, and in turn, promoted the invasion of lung cancer cells . Taken together, HCP5 up‐regulated the expression of Snail and Slug by sponging miR‐203 and activated the TGF‐β/SMAD signal pathway promoting metastasis of NSCLC.…”

Section: Main Molecular Mechanism Of Lncrna To Regulate the Metastasimentioning

confidence: 99%

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

Fang

Wang

Gong

et al. 2020

J Cellular Molecular Medi

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Non–small‐cell lung cancer (NSCLC) has become the most lethal human cancer because of the high rate of metastasis. Hence, clarifying the molecular mechanism underlying NSCLC metastasis is very important to improve the prognosis of patients with NSCLC. Long non‐coding RNAs (LncRNAs) are a class of RNA molecules longer than 200 nucleotides, which can participate in diverse biological processes. About 18% of human LncRNAs were recently found to be associated with tumours. Many studies indicated that aberrant expression of LncRNAs played key roles in the progression and metastasis of NSCLC. According to the function in tumours, LncRNAs can be divided into two classes: oncogenic LncRNAs and tumour‐suppressor LncRNAs. In this review, we summarized the main molecular mechanism of LncRNAs regulating NSCLC metastasis, including three aspects: (a) LncRNAs interact with miRNAs as ceRNAs; (b) LncRNAs bind with target proteins; and (c) LncRNAs participate in the transduction of different signal pathways. Then, LncRNAs can exert their function to regulate the metastasis of NSCLC through influencing the progression of epithelial‐mesenchymal transition (EMT) and the properties of cancer stem cell (CSC). But, it is necessary to do some further research to demonstrate the LncRNAs particular regulatory mechanism of inhibiting the metastasis of NSCLC and explore new drugs targeting LncRNAs.

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HCP5 is a SMAD3-responsive long non-coding RNA that promotes lung adenocarcinoma metastasis via miR-203/SNAI axis

Cited by 94 publications

References 49 publications

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis

Unique metastasis‐associated lncRNA signature optimizes prediction of tumor relapse in lung adenocarcinoma

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

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