HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis

Mu, Linsong; Wang, Yeli; Su, Hailong; Yuan, Lin; Sui, Wu; Yu, Xiang; Lv, Zhongchuan

doi:10.1007/s10620-020-06819-w

Cited by 28 publications

(23 citation statements)

References 33 publications

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“…Further expression analysis and survival analysis showed that only HIF1A-AS2 and RP11-366L20.2 fulfilled our criteria that they are highly expressed in tumors and that their high expression indicates a worse prognosis. It was reported that HIF1A-AS2 is up-regulated in GC tumorous tissues, and its overexpression promotes gastric cancer cell proliferation and metastasis and indicates poor prognosis ( Mu et al, 2021 ; Chen et al, 2015 ). RP11-366L20.2, also known as HMGA2-AS1, has been recognized as an oncogene in pancreatic cancer ( Ros et al, 2019 ) and osteosarcoma ( Rothzerg et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Nai

Zeng

et al. 2022

Front. Cell Dev. Biol.

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Gastric carcinoma is the fourth most prevalent cause of cancer-related deaths worldwide because of dismal prognosis and few therapeutic options. Accumulated studies have indicated that targeting lysyl oxidase (LOX) family members may serve as an anticancer strategy. Nevertheless, the specific mechanisms of LOX in stomach carcinoma are still unclear. In this study, we demonstrated that LOX is significantly different in 13 types of cancers and may act as a potential therapeutic target, especially in stomach carcinoma. Moreover, overexpression of LOX in gastric carcinoma was validated by multiple databases and contributed to the poor overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) of stomach adenocarcinoma (STAD) patients. Next, based on the ceRNA hypothesis, the HIF1A-AS2/RP11-366L20.2-miR-29c axis was characterized as the upstream regulatory mechanism of LOX gene overexpression in gastric cancer by combining correlation analysis, expression analysis, and survival analysis. Finally, we illustrated that LOX gene overexpression leads to dismal prognosis of gastric cancer, perhaps through promoting M2 macrophage polarization and tumor immune escape and enhancing drug resistance of tumor cells to chemotherapeutic drugs. Our research demonstrate that LOX may be potentially applied as a novel prognostic marker and targeting inhibition of LOX holds promise as a treatment strategy for gastric cancer.

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Section: Discussionmentioning

confidence: 99%

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Nai

Zeng

et al. 2022

Front. Cell Dev. Biol.

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“…PD-L1 expression was also higher in cluster 2 than in cluster 1. Previous studies revealed that multiple lncRNAs indirectly regulated PD-L1 expression to impact the survival of cancer patients ( Tian et al, 2021a ; Tian et al, 2021b ; Mu et al, 2021 ). We speculated that the expression profile of prognostic m6A-related lncRNAs in cluster 2 might increase PD-L1 expression, resulting in worse OS.…”

Section: Discussionmentioning

confidence: 99%

Relationships of N6-Methyladenosine-Related Long Non-Coding RNAs With Tumor Immune Microenvironment and Clinical Prognosis in Lung Adenocarcinoma

et al. 2021

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Background: Lung adenocarcinoma (LUAD) is the major subtype of lung cancer and is associated with very high mortality. Emerging studies have shown that N6-methyladenosine (m6A)-related long non-coding (lnc) RNAs play crucial roles in tumor prognosis and the tumor immune microenvironment (TME). We aimed to explore the expression patterns of different m6A-related lncRNAs concerning patient prognosis and construct an m6A-related lncRNA prognostic model for LUAD.Methods: The prognostic value of m6A-related lncRNAs was investigated in LUAD samples from The Cancer Genome Atlas (TCGA). Potential prognostic m6A-related lncRNAs were selected by Pearson’s correlation and univariate Cox regression analysis. Patients were divided into clusters using principal component analysis and the m6A-related lncRNA prognostic signature was calculated using least absolute shrinkage and selection operator (LASSO) Cox regression analysis.Results: Based on 91 prognostic m6A-related lncRNAs, we identified two m6A-related-lncRNA pattern clusters with different overall survival (OS) and different TMEs. We subsequently verified our findings multidimensionally by constructing a 13 m6A-related lncRNA prognostic signature (m6A-LPS) to calculate the risk score, which was robust in different subgroups. The receiver operating characteristic (ROC) curves and concordance index demonstrated that m6A-LPS harbored a promising ability to predict OS in TCGA data set and independent GSE11969 cohort. The risk score was also related to OS, TME, and clinical stage, and the risk score calculated by our model was also identified as independent prognostic predictive factors for LUAD patients after adjustment for age, smoking, gender, and stage. Enrichment analysis indicated that malignancy and drug resistance-associated pathways were more common in cluster2 (LUAD-unfavorable m6A-LPS). Furthermore, the results indicated that the signaling pathway enriched by the target gene of 13 m6A-related lncRNAs may be associated with metastasis and progression of cancer according to current studies.Conclusion: The current results indicated that different m6A-related-lncRNA patterns could affect OS and TME in patients with LUAD, and the prognostic signature based on 13 m6A-related lncRNAs may help to predict the prognosis in LUAD patients.

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“… 19 Consistently, HIF1A-AS2 contributed to proliferation, metastasis, and tumorigenesis of LUAD cells, indicating that HIF1A-AS2 is a positive regulator in the development of LUAD. It has been reported that there is an association of high HIF1A-AS2 expression with shorter OS in triple-negative breast cancer, 13 gastric cancer, 20 and bladder cancer. 10 In the clinical samples, HIF1A-AS2 was upregulated in LUAD tissues and was associated with an unfavorable prognosis in LUAD patients.…”

Section: Discussionmentioning

confidence: 99%

HIF1A-AS2 induces osimertinib resistance in lung adenocarcinoma patients by regulating the miR-146b-5p/IL-6/STAT3 axis

et al. 2021

Molecular Therapy - Nucleic Acids

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Although epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) show efficacy in lung adenocarcinoma (LUAD) patients, TKI resistance inevitably develops, limiting long-term results. Thus, there is an urgent need to address drug resistance in LUAD. Long non-coding RNA (lncRNA) HIF1A-AS2 could be a critical mediator in the progression of various tumor types. We examined the function of HIF1A-AS2 in modifying tumor aggravation and osimertinib resistance in lung adenocarcinoma. Using clinical samples, we showed that HIF1A-AS2 was upregulated in LUAD specimens, predicting poorer overall survival and disease-free survival. HIF1A-AS2 silencing inhibited the proliferation, migration, and tumorigenesis of LUAD cells and therapeutic efficacy of osimertinib against tumor cells in vitro and in vivo . RNA precipitation assays, western blotting, luciferase assays, and rescue experiments demonstrated that HIF1A-AS2 sponged microRNA-146b-5p (miR-146b-5p), promoting interleukin-6 (IL-6) expression, activating the IL-6/STAT3 pathway, and leading to LUAD progression. miR-146b-5p and IL-6 levels were correlated with the prognosis of LUAD patients. Our results indicated that HIF1A-AS2 functions as an oncogenic factor in adenocarcinoma cells by targeting the miR-146b-5p/IL-6/STAT3 axis and may be a prognostic indicator of survival. Moreover, it can be a potential therapeutic target to enhance the efficacy of osimertinib in LUAD patients.

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HIF1A-AS2 Promotes the Proliferation and Metastasis of Gastric Cancer Cells Through miR-429/PD-L1 Axis

Cited by 28 publications

References 33 publications

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

lncRNA/miR-29c-Mediated High Expression of LOX Can Influence the Immune Status and Chemosensitivity and Can Forecast the Poor Prognosis of Gastric Cancer

Relationships of N6-Methyladenosine-Related Long Non-Coding RNAs With Tumor Immune Microenvironment and Clinical Prognosis in Lung Adenocarcinoma

HIF1A-AS2 induces osimertinib resistance in lung adenocarcinoma patients by regulating the miR-146b-5p/IL-6/STAT3 axis

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