SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A

Ji, Hao; Wang, Juan; Lu, Binfeng; Li, Juan; Zhou, Jing; Wang, Li; Xu, Shiwen; Peng, Peng; Hu, Xuezhen

doi:10.1186/s10020-020-00222-x

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…It has been demonstrated that many cytoplasmic lncRNAs act as competing endogenous RNAs (ceRNAs) via binding miRNAs ( 24 ). In ICC, several lncRNAs such as lncRNA MT1JP and lncRNA AGAP2-AS1 have been shown to exhibit their tumor-related effects via sponging miRNAs to modulate the expression of various genes involved in tumor progression ( 25 , 26 ). Previously, SNHG12 was also reported to act as a ceRNA in several tumors, such as cervical cancer and oral squamous cell carcinoma ( 19 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells

Yang

Wang

et al. 2021

Front. Med.

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Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC.

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Section: Discussionmentioning

confidence: 99%

Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells

Yang

Wang

et al. 2021

Front. Med.

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“…We found that AGAP2-AS1 modulated the proliferation, migration and invasion of CCA, and Ji et al. confirmed that SP1-induced AGAP2-AS1 promoted CCA proliferation by silencing CDKN1A ( 47 ). Therefore, both GOLGA7B and AGAP2−AS1 regulate CCA progression and are potential therapeutic targets for CCA.…”

Section: Discussionmentioning

confidence: 54%

Identification of therapeutic targets and prognostic biomarkers in cholangiocarcinoma via WGCNA

Xiao

et al. 2022

Front. Oncol.

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BackgroundCholangiocarcinoma (CCA) is a highly aggressive malignant tumor for which limited treatment methods and prognostic signatures are available. This study aims to identify potential therapeutic targets and prognostic biomarkers for CCA.MethodsBased on differentially expressed genes (DEGs) identified from The Cancer Genome Atlas (TCGA) data, our study identified key gene modules correlated with CCA patient survival by weighted gene coexpression network analysis (WGCNA). Cox regression analysis identified survival-related genes in the key gene modules. The biological properties of the survival-related genes were evaluated by CCK-8 and transwell assays. Then, these genes were used to construct a prognostic signature that was internally and externally validated. Additionally, by combining clinical characteristics with the gene−based prognostic signature, a nomogram for survival prediction was built.ResultsWGCNA divided the 1531 DEGs into four gene modules, and the yellow gene module was significantly associated with overall survival (OS) and histologic neoplasm grade. Our study identified the lncRNA AGAP2−AS1 and a novel gene, GOLGA7B, that are closely related to survival. GOLGA7B downregulation promoted the invasion, migration and proliferation of CCA cells, but AGAP2−AS1 had the opposite effect. AGAP2−AS1 and GOLGA7B were integrated into a gene−based prognostic signature, and both internal and external validation studies confirmed that this two-gene prognostic signature and nomogram could accurately predict CCA patient prognosis.ConclusionAGAP2−AS1 and GOLGA7B are potential therapeutic targets and prognostic biomarkers for CCA.

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“…[25][26][27] Our group's previous research has already known that multiple lncRNAs are involved in the regulation of the biological functions of CRC, pancreatic cancer, and cholangiocarcinoma. 12,13,28 In the present study, we screened the differentially expressed lncRNA linc02231 in CRC from the GEO database. as ceRNAs to regulate the expression of miRNAs, leading to the silencing of downstream target genes.…”

Section: Discussionmentioning

confidence: 99%

“…lncRNAs not only participate in the regulation of various molecular pathways in tumor cells, but also in the modulation of the immune microenvironment, such as immune cell infiltration, extracellular matrix and cancer‐associated fibroblasts 25–27 . Our group's previous research has already known that multiple lncRNAs are involved in the regulation of the biological functions of CRC, pancreatic cancer, and cholangiocarcinoma 12,13,28 …”

Section: Discussionmentioning

confidence: 99%

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

Fang

Chang

et al. 2023

The Journal of Gene Medicine

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Background Long non‐coding RNAs (lncRNAs) play a critical role in regulating various human diseases including cancer. In colorectal cancer (CRC), there are still some undervalued lncRNAs with potential functions and mechanisms that need to be clarified. The present study aimed to investigate the role of linc02231 in the progression of CRC. Methods The proliferation of CRC cells was evaluated using Cell Counting Kit‐8, colony formation, and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays. Cell migration was examined through wound healing and Transwell analyses. The impact of linc02231 on angiogenesis was determined through a tube formation assay. Western blotting was used to detect the expression of specific proteins. A mouse xenograft model is established to observe the effect of linc02231 on the in vivo growth of CRC cells. Target genes of linc02231 are screened using high‐throughput sequencing. The transcriptional activity of STAT2 on linc02231 and the binding activity between linc02231/miR‐939‐5p/hnRNPA1 were analyzed by a luciferase assay. Results Based on public databases and comprehensive bioinformatics analysis, we found that lncRNA linc02231 was upregulated in CRC tumor tissues, which is consistent with our clinical results. linc02231 promoted the proliferation and migration of CRC cells in vitro and their tumorigenicity in vivo. Furthermore, linc02231 promotes the angiogenic ability of human umbilical vein endothelial cells. Mechanistically, the transcription factor STAT2 binds to the promoter region of linc02231 and activates its transcription. linc02231 also competes with miR‐939‐5p for binding to the pro‐oncogenic target gene hnRNPA1, preventing its degradation. hnRNPA1 prevents the maturation of angiopoietin‐like protein 4 (ANGPTL4) messenger RNA, leading to impaired tumor angiogenesis and increased metastasis of CRC. Conclusions The expression of linc02231, which is induced by STAT2, has been found to enhance the proliferation, metastasis, and angiogenesis of CRC by binding to miR‐939‐5p and increasing the expression of hnNRPA1 at the same time as suppressing ANGPTL4. These findings suggest that linc02231 could serve as a potential biomarker and therapeutic target for CRC.

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SP1 induced long non-coding RNA AGAP2-AS1 promotes cholangiocarcinoma proliferation via silencing of CDKN1A

Cited by 10 publications

References 30 publications

Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells

Long Non-coding RNA SNHG12, a New Therapeutic Target, Regulates miR-199a-5p/Klotho to Promote the Growth and Metastasis of Intrahepatic Cholangiocarcinoma Cells

Identification of therapeutic targets and prognostic biomarkers in cholangiocarcinoma via WGCNA

STAT2‐induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer

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