LncRNA HOTTIP inhibits cell pyroptosis by targeting miR‐148a‐3p/AKT2 axis in ovarian cancer

Tan, Cai; Liu, Wei; Zheng, Zhihua; Wan, Xiaogang

doi:10.1002/cbin.11588

Cited by 58 publications

(53 citation statements)

References 40 publications

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“…Several reports have demonstrated that lncRNAs regulate the mediators of pyroptosis, including NLR family pyrin domain containing 1 (NLRP1) ( 26 ), NLR family pyrin domain containing 3 (NLRP3) ( 27 ), Casp1 ( 28 ) and Casp3 ( 29 ). Nevertheless, the non-coding RNAs that regulate GSDMs, the key execution proteins of pyroptosis have not been identified.…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)-induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non-coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR-induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)-448 and gasdermin E (GSDME) levels were evaluated using reverse transcription-quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR-448 and GSDME was assessed using the dual-luciferase reporter assay. Pyroptosis was examined using phase-contrast microscopy, flow cytometry, Cell Counting Kit-8 assay and lactate dehydrogenase release assay. IR dose-dependently induced GSDME-mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR-448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR-448 expression. Notably, NEAT1 knockdown suppressed IR-induced pyroptosis, full-length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR-induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR-induced pyroptosis and viability in HCT116 cells via miR-448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR-induced pyroptosis.

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Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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“…Wang et al (2021) revealed that lncRNA XIST promoted pyroptosis through the XIST/miR-150-5p/c-Fos axis, and Wan et al (2020) discovered that lncRNA-H19 significantly promoted NLRP3/6 inflammasome imbalance and induced pyroptosis of microgliocyte. Furthermore, Tan et al (2021) found that LncRNA HOTTIP could inhibit pyroptosis of ovarian cancer cells by targeting the miR-148a-3p/AKT2 axis. However, there are limited studies focusing on pyroptosis-associated lncRNAs in BC.…”

Section: Introductionmentioning

confidence: 99%

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer

Ping

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Background: Pyroptosis, a kind of programmed cell death characterized by the rupture of cell membranes and the release of inflammatory substances, plays an important role in the occurrence and development of cancer. However, few studies focus on the pyroptosis-associated long non-coding RNAs (lncRNAs) in breast cancer (BC). The prognostic value of pyroptosis-associated lncRNAs and their relationship with tumor microenvironment (TME) in BC remain unclear. The purpose of this study was to explore the prognostic role of pyroptosis-associated lncRNAs and their relationship with TME in BC.Methods: The transcriptome data and clinical data of female BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 937 patients were randomly assigned to either training set or validation set. A pyroptosis-associated lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis and immune microenvironment analysis related to pyroptosis-associated lncRNAs were performed. A nomogram based on the risk score and clinical characteristics was established.Results: A 9-pyroptosis-associated lncRNA signature was constructed to separate BC patients into two risk groups. High-risk patients had poorer prognosis than low-risk patients. The risk score was proven to be an independent prognostic factor by multivariate Cox regression analysis. Function analysis and immune microenvironment analysis showed that low-risk BC tended to be an immunologically “hot” tumor. A nomogram was constructed with risk score and clinical characteristics. Receiver operating characteristic curve (ROC) analysis demonstrated credible predictive power of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.880 at 1 year, 0.804 at 3 years, and 0.769 at 5 years in the training set, and 0.799 at 1 year, 0.794 at 3 years, and 0.728 at 5 years in the validation set.Conclusion: We identified a novel pyroptosis-associated lncRNA signature that was an independent prognostic indicator for BC patients. Pyroptosis-associated lncRNAs had potential relationship with the immune microenvironment and might be therapeutic targets for BC patients.

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“… 11 A study showed that lncRNA HOTTIP holds up ovarian cancer cell pyroptosis by modulating the miR-148a-3p/AKT2 signaling pathway. 12 In addition, another work showed that lncRNA ADAMTS9-AS2 induces pyroptotic cell death and strengthens gastric cancer cells’ sensitivity to cisplatin. 13 Moreover, downregulation of lncRNA XIST restrained non-small cell lung cancer multiplication through irritating pyroptosis.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Pyroptosis-Related lncRNAs Associated with the Prognosis of Breast Cancer Through Interactive Analysis

Gao¹,

Li²

2021

CMAR

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Background The role of pyroptosis and lncRNAs in breast cancer remains controversial. This study aimed to explore the pyroptosis-related lncRNAs in breast cancer. Methods All the data used for bioinformatics analysis were downloaded from The Cancer Genome Atlas database. Limma package was used to perform difference analysis, and distinguish mRNA and lncRNA. Survival package was used to conduct prognosis analysis. LASSO algorithm, univariate cox analysis and multivariate cox analysis were used to construct the prognosis model. P value <0.05 was regarded as statistically significant. Results Based on the seven pyroptosis-related lncRNAs tightly associated with patients’ prognosis, a prognostic prediction model was finally developed, which showed powerful effectiveness (Training cohort, one-year AUC = 0.82, 95% Cl = 0.69–0.95, three-year AUC = 0.77, 95% Cl = 0.68–0.85, five-year AUC = 0.74, 95% Cl = 0.66–0.82; Validation cohort, one-year AUC = 0.68, 95% Cl = 0.53–0.84, three-year AUC = 0.72, 95% Cl = 0.64–0.81, five-year AUC = 0.67, 95% Cl = 0.57–0.77). GSEA analysis demonstrated that the protein secretion, angiogenesis, TGF-β signaling and MTORC1 signaling might be involved in the high-risk patients. Moreover, immune infiltration analysis showed that the risk score was positively correlated with Tgd and Th2 cells, yet negatively correlated with CD8+ T cells, cytotoxic cells and T helper cells, which might partly explain the poor prognosis of high-risk patients. Finally, the expression level of seven model lncRNAs in the real world was validated by qRT-PCR using four cancer cell lines (MCF-7, T47D, MDA-MB-231, MDA-MB-469). Conclusion In conclusion, our study identified lncRNAs that are remarkably correlated with patients’ survival and might participate in the pyroptosis process, which might be underlying tumor biomarker and therapeutic targets. This study may provide direction for future research.

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LncRNA HOTTIP inhibits cell pyroptosis by targeting miR‐148a‐3p/AKT2 axis in ovarian cancer

Cited by 58 publications

References 40 publications

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer

Identification of Novel Pyroptosis-Related lncRNAs Associated with the Prognosis of Breast Cancer Through Interactive Analysis

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