LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway

Shen, Yueming; Liu, Yingying; Sun, Ting; Yang, Wei

doi:10.1016/j.yexcr.2017.06.016

Cited by 56 publications

(34 citation statements)

References 44 publications

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“…has been reported to be associated with cellular apoptosis (26). To determine if lincRNA-p21 was involved in hypoxia/SD-induced apoptosis, its expression was evaluated in MSCs exposed to hypoxia/SD for 24 h. lincRNA-p21 was significantly increased in MSCs following hypoxia/SD treatment, as demonstrated by RT-qPCR analysis ( Fig.…”

Section: Mif Protects Mscs From Hypoxia/sd-induced Apoptosis By Inhibmentioning

confidence: 80%

Role of lincRNA‑p21 in the protective effect of macrophage inhibition factor against hypoxia/serum deprivation‑induced apoptosis in mesenchymal stem cells

2018

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Stem cell transplantation is a promising clinical strategy for curing ischemic cardiomyopathy. However, its efficacy is impaired by low cell survival following transplantation, partly caused by insufficient resistance of the transplanted stem cells to severe oxidative stress at the injury site. In the current study, it was demonstrated that the small‑molecule macrophage migration inhibitory factor (MIF) enhanced the defense of bone marrow‑derived mesenchymal stem cells (MSCs) against hypoxia/serum deprivation (SD)‑induced apoptosis in vitro. MIF significantly suppressed apoptosis and caspase family activities through inhibition of long intergenic noncoding (linc) RNA‑p21 to maintain activation of the Wnt/β‑catenin signaling pathway. The regulatory loop between MIF and the lincRNA‑p21‑Wnt/β‑catenin signaling pathway was identified to be associated with the inhibition of oxidative stress. The involvement of the lincRNA‑p21‑Wnt/β‑catenin signaling pathway in the effects of MIF in MSCs by overexpression of lincRNA‑p21and silencing β‑catenin using small interfering RNA was also demonstrated, both of which abolished the anti‑apoptotic and anti‑oxidative effects of MIF in MSCs under hypoxia/SD conditions. In conclusion, MIF protected MSCs from hypoxia/SD‑induced apoptosis by interacting with lincRNA‑p21, leading to activation of the downstream Wnt/β‑catenin signaling pathway and decreased oxidative stress. Thus, treatment with MIF may have important therapeutic implications in improving MSC survival and therapeutic efficiency.

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Section: Mif Protects Mscs From Hypoxia/sd-induced Apoptosis By Inhibmentioning

confidence: 80%

Role of lincRNA‑p21 in the protective effect of macrophage inhibition factor against hypoxia/serum deprivation‑induced apoptosis in mesenchymal stem cells

2018

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“…These RNAs control many cellular functions by interaction with chromatin-modifying complex, regulation of transcriptional enhancers, and posttranscriptional regulation (18). LncRNAs were found to be involved in DDR by regulating the expressions of DDR relevant genes, and the inhibition of lncRNAs expressions improved the radiosensitivity of some cancers (19)(20)(21)(22). Our study investigated whether lncRNAs were involved in the radioresponse in esophageal cancer cells for the first time.…”

Section: A C D Bmentioning

confidence: 93%

Cancer-associated Fibroblast–promoted LncRNA DNM3OS Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

Zhang

Hua

Jiang

et al. 2019

Clinical Cancer Research

128

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Purpose: Our study aimed to investigate whether CAF (cancer-associated fibroblasts) were involved in long noncoding RNAs (lncRNA)-regulated radioresponse in esophageal squamous cell carcinoma (ESCC). Experimental Design: By use of lncRNAs PCR array, 38 lncRNAs were screened in esophageal cancer cells and in normal esophageal epithelial cells Het-1A. LncRNA DNM3OS was detected in tumor tissues of patients with ESCC and in matched normal esophageal epithelial tissues by qRT-PCR analysis and in situ hybridization assay. The association of DNM3OS and tumor radioresistance was investigated in vitro and in vivo. The influences of DNM3OS on DNA damage response (DDR) was investigated by Western blotting, immunofluorescence imaging, and comet assay. The mechanisms by which CAFs promoted DNM3OS expression was investigated by kinase inhibitors' screening, luciferase assay, and chromatin immunoprecipitation. Results: Among the 38 lncRNAs tested, DNM3OS was found to have a much higher expression level in esophageal cancer cells than in Het-1A. In tumor tissues of 16 patients with ESCC, the expression level of DNM3OS showed an average increase of 6.3429-fold compared with that in matched normal tissues. DNM3OS conferred significant radioresistance in vitro and in vivo by regulating DDR. CAFs promoted the expression of DNM3OS with a 39.2554-fold and 38.3163-fold increase in KYSE-30 and KYSE-140, respectively. CAFs promoted the expression of DNM3OS in a PDGFb/PDGFRb/ FOXO1 signaling pathway-dependent manner. FOXO1, a transcription factor downstream of PDGFb/PDGFRb signaling pathway, initiated the transcription of DNM3OS by binding to DNM3OS promoter. Conclusions: Our study highlighted CAF-promoted DNM3OS as an attractive target to reverse tumor radioresistance in ESCC.

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“…It has been acknowledged that AKT/mTOR pathway performs essential part in regulating cancer cell biological activities such as proliferation and migration [12], including in CC [23]. Therefore, we speculated whether GHET1 exerted its influence through regulating AKT/mTOR pathway.…”

Section: Knockdown Of Ghet1 Suppressed Akt/mtor and Wnt/β-catenin Patmentioning

confidence: 95%

LncRNA GHET1 promotes cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways

Liu

Luo

et al. 2020

Bioscience Reports

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Cervical cancer (CC) is a prevalent gynecological cancer, and the patients with CC usually suffer from dismal prognosis. Long non-coding RNAs (lncRNAs) are demonstrated to serve as promising biological targets in human cancers. Gastric carcinoma proliferation enhancing transcript 1 (GHET1) has been revealed to function as an oncogene in several cancers, but it has never been investigated in CC. We proposed to examine the biological role of GHET1 in CC and the underlying mechanism and validated the up-regulated expression of GHET1 in CC cell lines. Loss-of-function assays demonstrated that down-regulation of GHET1 inhibited cell growth, migration and epithelial-to-mesenchymal transition (EMT) in CC. Furthermore, we validated that GHET1 down-regulation could inactivate AKT/mTOR and Wnt/β-catenin pathways, and that respective activation of these two pathways abrogated the inhibitive effect of GHET1 knockdown on CC cell growth, migration and EMT. Moreover, we unfolded a preliminary investigation on the modulation of GHET1 on AKT/mTOR and Wnt/β-catenin pathways. We found that GHET1 stabilized E2F6 mRNA through interacting with IGF2BP2, so as to regulate the activity of AKT/mTOR and Wnt/β-catenin pathways. Rescue assays also proved that GHET1 regulated these two pathways and CC cell growth, migration and EMT through E2F6. In conclusion, we revealed that down-regulation of GHET1 suppresses cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways, indicating GHET1 as a promising molecular biomarker for CC treatment improvement.

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LincRNA-p21 knockdown enhances radiosensitivity of hypoxic tumor cells by reducing autophagy through HIF-1/Akt/mTOR/P70S6K pathway

Cited by 56 publications

References 44 publications

Role of lincRNA‑p21 in the protective effect of macrophage inhibition factor against hypoxia/serum deprivation‑induced apoptosis in mesenchymal stem cells

Role of lincRNA‑p21 in the protective effect of macrophage inhibition factor against hypoxia/serum deprivation‑induced apoptosis in mesenchymal stem cells

Cancer-associated Fibroblast–promoted LncRNA DNM3OS Confers Radioresistance by Regulating DNA Damage Response in Esophageal Squamous Cell Carcinoma

LncRNA GHET1 promotes cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways

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