Long noncoding RNA HAR1A regulates oral cancer progression through the alpha-kinase 1, bromodomain 7, and myosin IIA axis

Lee, Chi‐Pin; Ko, Albert Min-Shan; Nithiyanantham, Srinivasan; Lai, Chu-Hu; Ko, Ying‐Chin

doi:10.1007/s00109-021-02095-x

Cited by 18 publications

(18 citation statements)

References 45 publications

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“…Lee et al [ 29 ] screened 83 long noncoding RNA arrays stimulated with monosodium urate in monocytes and suggested that HAR1A interacted with ALPK1. In the nucleus of cancer cells, HAR1A functioned upstream of the signaling pathway, and knockdown of HAR1A promoted ALPK1 expression and downregulated myosin IIA and BRD7, leading to inflammation and oral cancer progression.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of the Role of Alpha-Protein Kinase 1 in Cancer and Cancer-Related Inflammatory Diseases

2022

Cancers

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Background: Deregulation of conventional protein kinases is associated with the growth and development of cancer cells. Alpha-kinase 1 (ALPK1) belongs to a newly discovered family of serine/threonine protein kinases with no sequence homology to conventional protein kinases, and its function in cancer is poorly understood. Methods: In this systematic review, we searched for and analyzed studies linking ALPK1 to cancer development and progression. Results: Based on the current evidence obtained using human, animal, cellular, and tissue models, ALPK1 is located upstream and triggers cancer cell development and metastasis by regulating the inflammatory response through phosphorylation. Its mRNA and protein levels were found to correlate with advanced tumor size and lymph node metastasis, which occur from the cellular cytoplasm into the nucleus. ALPK1 is also strongly associated with gout, chronic kidney disease, and diabetes, which are considered as inflammatory diseases and associated with cancer. Conclusion: ALPK1 is an oncogene involved in carcinogenesis. Chronic inflammation is the common regulatory mechanism between cancer and these diseases. Future research should focus on identifying inhibitors of serine/threonine and ALPK1 at their phosphorylation sites, which would block various signal transductions and potentially offer kinase-targeted therapeutic agents for patients with cancer and inflammatory diseases.

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Section: Resultsmentioning

confidence: 99%

Systematic Review of the Role of Alpha-Protein Kinase 1 in Cancer and Cancer-Related Inflammatory Diseases

2022

Cancers

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“…Thus far, there are very few publications available regarding this molecule. HAR1A acted as a tumor suppressor for oral cancer by regulating the ALPK1/BRD7/myosin IIA axis in oral cancer [ 13 ]. Its tumor-suppressing potentials were also demonstrated in hepatocellular carcinoma (HCC) [ 14 ], and diffuse glioma [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…The results indicated that ectopic expression of HAR1A inhibited NSCLC cell proliferation in vitro and growth of NSCLC tumor xenograft and vice versa. Recently, Lee et al reported that lncRNA HAR1A suppressed oral cancer progression [ 13 ]. Collectively, these indicate that HAR1A plays a tumor-suppressive role in tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…By exploiting public databases, we find that lncRNA Highly Accelerated Region 1A ( HAR1A ), mapped to chromosome 20q13.33, was significantly less abundant in cancerous tissues than normal tissues and negatively associated with overall survival in LUAD. There are very few publications regarding this molecule to date, but several studies have suggested HAR1A as a tumor suppressor in oral cancer [ 13 ], hepatocellular carcinoma (HCC) [ 14 ], and diffuse glioma [ 15 ]. In this study, we performed bioinformatic analysis, followed by in vitro and in vivo invalidations to explore the implications of this lncRNA in LUAD.…”

Section: Introductionmentioning

confidence: 99%

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LncRNA HAR1A Suppresses the Development of Non-Small Cell Lung Cancer by Inactivating the STAT3 Pathway

Cao

Ling

et al. 2022

Cancers

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It is imperative to advance the understanding of lung cancer biology. The Cancer Genome Atlas (TCGA) dataset was used for bioinformatics analysis. CCK-8 assay, flow cytometry, and western blot were performed in vitro, followed by in vivo study. We found that lncRNA Highly Accelerated Region 1A (HAR1A) is significantly downregulated in lung adenocarcinoma (LUAD) and negatively associated with prognosis. We improved the prognostic accuracy of HAR1A in LUAD by combining genes regulating cell apoptosis and cell cycle to generate a 23-gene signature. Nomogram and decision curve analysis (DCA) confirmed that the gene signature performed robustly in predicting overall survival. Gene set variation analysis (GSVA) demonstrated several significantly upregulated malignancy-related events in the high-risk group, including DNA replication, DNA repair, glycolysis, hypoxia, MYC targets v2, and mTORC1. The risk signature distinguished LUAD patients suitable for chemotherapies or targeted therapies. Additionally, the knockdown of HAR1A accelerated NSCLC cell proliferation but inhibited apoptosis and vice versa. HAR1A regulated cellular activities through the STAT3 signaling pathway. The tumor-suppressing role of HAR1A was verified in the mouse model. Overall, the gene signature was robustly predictive of prognosis and sensitivity to anti-tumor drugs. HAR1A functions as a tumor suppressor in NSCLC by regulating the STAT3 signaling pathway.

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“…In addition, it was found that high expression of LBX2-AS1 in glioma patients was associated with poor prognosis (35). HAR1A is a tumor suppressor, and in oral cancer patients, knockdown of HAR1A promotes the expression of ALPK1 and leads to oral cancer progression (36). According to Dong et al, SNHG14 plays a critical role in the mechanism of drug resistance in breast cancer, and knockdown of SNHG14 significantly improves trastuzumab efficacy in breast cancer patients (37).…”

Section: Discussionmentioning

confidence: 99%

A Novel Necroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Response of Glioma

Liu

et al. 2022

BioMed Research International

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Glioma is one of the most common intracranial malignancies that plagues people around the world. Despite current improvements in treatment, the prognosis of glioma is often unsatisfactory. Necroptosis is a form of programmed cell death. As research progresses, the role of necroptosis in tumors has gradually attracted the attention of researchers. And lncRNA is regarded as a critical role in the development of cancer. Therefore, this study is aimed at establishing a prognostic model based on necroptosis-associated lncRNAs to accurately assess the prognosis and immune response of patients with glioma. The RNA sequences of glioma patients and normal brain samples were downloaded from The Cancer Genome Atlas (TCGA) and GTEx databases, respectively. The coexpression analysis was performed to identify the necroptosis-related lncRNAs. Then, we utilized LASSO analysis following univariate Cox analysis to construct a prognostic model. Subsequently, we applied the Kaplan-Meier curve, time-dependent receiver operating characteristics (ROC), and univariate and multivariate Cox regression analyses to assess the effectiveness of this model. And the functional enrichment analyses and immune-related analyses were employed to investigate the potential biological functions. A validation set was obtained from the Chinese Glioma Genome Atlas (CGGA) database. And qRT-PCR was employed to further validate the expression levels of selected necroptosis-associated lncRNAs. Seven necroptosis-related lncRNAs (FAM13A-AS1, JMJD1C-AS1, LBX2-AS1, ZBTB20-AS4, HAR1A, SNHG14, and LINC00900) were determined to construct a prognostic model. The area under the ROC curve (AUC) was 0.871, 0.901, and 0.911 at 1, 2, and 3 years, respectively. The risk score was shown to be an important independent predictor in both univariate and multivariate Cox regression analyses. Through functional enrichment analyses, we found that the differentially expressed genes (DEGs) were mainly enriched in protein binding and signaling-related biological functions and immune-associated pathways. In conclusion, we established and validated a novel necroptosis-related lncRNA signature, which could accurately predict the overall survival of glioma patients and serve as potential therapeutic targets.

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Long noncoding RNA HAR1A regulates oral cancer progression through the alpha-kinase 1, bromodomain 7, and myosin IIA axis

Cited by 18 publications

References 45 publications

Systematic Review of the Role of Alpha-Protein Kinase 1 in Cancer and Cancer-Related Inflammatory Diseases

Systematic Review of the Role of Alpha-Protein Kinase 1 in Cancer and Cancer-Related Inflammatory Diseases

LncRNA HAR1A Suppresses the Development of Non-Small Cell Lung Cancer by Inactivating the STAT3 Pathway

A Novel Necroptosis-Related lncRNA Signature for Predicting Prognosis and Immune Response of Glioma

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