Epigenetic induction of tumor stemness via the lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma

Xu, Fan; Liu, Zhonghe; Liu, Ronghua; Chen, Lu; Wang, Lin; Mao, Wei; Zhu, Qinqing; Shou, Huankai; Zhang, Xiaoying; Li, Yin; Chu, Yiwei; Gu, Jie

doi:10.1186/s12964-020-0510-8

Cited by 23 publications

(16 citation statements)

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“…TET3 expression was elevated with lipopolysaccharide stimulation via p38/ERK-MAPK pathway in ESCC and negatively correlated with patients' survival. TET3 induced the stemness of ESCC cells (Xu et al, 2020). Our results indicated that TET3 declined in TGF-β1 stimulation and TET3 overexpression inhibited TGF-β1-induced EMT and EMT-mediated metastasis of SKOV3 and 3AO cells by demethylating miR-30d precursor gene, indicating a novel mechanism of epigenetic regulation in ovarian cancer.…”

Section: Introductionmentioning

confidence: 62%

LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

et al. 2021

Preprint

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Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis and could function as competing endogenous RNAs (ceRNAs) to regulate microRNAs (miRNAs). LncRNA small nucleolar RNA host gene 8 (LncRNA SNHG8) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the molecular mechanisms by which lncRNA SNHG8 contributes to hepatocellular carcinoma (HCC) still remains unclear. In the present study, we reported that lncRNA SNHG8 was abnormally up-regulated in liver cancer tissues and HCC cell lines. Moreover, knockdown of lncRNA SNHG8 significantly attenuated the proliferation, migration, invasion process of HCC cell line HepG2 in vitro. Mechanistically, we first reported that suppression of lncRNA SNHG8 evidently enhanced miR-542-3p and miR-4701-5p expression and decreased TET3 expression at posttranscriptional level. Furthermore, lncRNA SNHG8 upregulated TET3 expression by sponging miR-542-3p and miR-4701-5p by competing binding. Taken together, our results confirmed the oncogene role of lncRNA SNHG8 and discovered the underlying mechanism that lncRNA SNHG8 upregulated TET3 through the sponging or decaying of miR-542-3p and miR-4701-5p in human hepatocellular carcinoma, suggesting that lncRNA SNHG8 may serve as a potential diagnostic marker and therapeutic target for patients with hepatocellular carcinoma.

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Section: Introductionmentioning

confidence: 62%

LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

et al. 2021

Preprint

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“…2 b), suggesting that LPS was correlated with cell stemness. LPS was reported to upregulate pluripotent marker expression and induce cell stemness [ 29 , 30 ]. qRT-PCR assays revealed that the pluripotent markers Nanog, Sox2, cMyc, Klf4, and Fgf5 were significantly increased, and markers associated with stem cells, such as CD34, CD45, CD90, Tert, and Sox9, were also upregulated in AML12 cells after the administration of LPS (Fig.…”

Section: Resultsmentioning

confidence: 99%

The stemness of hepatocytes is maintained by high levels of lipopolysaccharide via YAP1 activation

et al. 2021

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Background The liver possesses a powerful regeneration ability, which is correlated with the stemness of hepatocytes in the portal vein (PV). However, the mechanism underlying the maintenance of hepatocyte stemness has not been elucidated. Here, we hypothesized that high levels of lipopolysaccharide from the portal vein might maintain the stemness of hepatocytes in the PV area. Methods First, we examined the location of hepatic stem cells and the concentration of lipopolysaccharide (LPS) in the portal vein and inferior vena cava. Then, we assessed the effect of LPS on stemness maintenance in mice by using antibiotics to eliminate LPS and knocking out the LPS receptor, TLR4. In vitro, the effect of LPS on the stemness of hepatocytes was investigated by colony and sphere formation assays and assessment of pluripotent and stem cell marker expression. Furthermore, we studied the mechanism by which LPS regulates the stemness of hepatocytes. Finally, we ligated the portal vein branch to further verify the effect of LPS. Results We found that a high level of LPS from the portal vein was correlated with the location of hepatic stem cells in the PV area, and elimination of LPS by antibiotics inhibited the expression of the stemness marker. LPS promoted colony and sphere formation and induced the upregulation of pluripotent and stem cell markers in AML12 cells. Furthermore, in the reprogramming medium, LPS facilitated the dedifferentiation of mature hepatocytes into hepatic progenitor-like cells, which exhibited a bipotent differentiation capacity in vivo and in vitro. Mechanistically, LPS bound TLR4 to regulate stemness of hepatocytes via the activation of YAP1 signaling, and blockade of YAP1 abolished the LPS-induced cell stemness and upregulation of pluripotent markers. Conclusions Our study implies a correlation between LPS/TLR4/YAP1 signaling and cell stemness, and LPS was shown to be involved in stemness maintenance of hepatocytes in the PV area. LPS might be used to induce the dedifferentiation of mature hepatocytes into progenitor-like cells for repair of liver injury.

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“…Higher TET3 is correlated with higher stage and poor clinicopathological features [ 40 ]. Lipopolysaccharide induces the dryness of esophageal squamous cell carcinoma cells by activating the LPS-TET3-HOXB2 signal axis [ 41 ]. In this study, the expression of TET3 in PTC and its relationship with the biological behavior of cancer cells were discussed for the first time.…”

Section: Discussionmentioning

confidence: 99%

TET3 Mediates 5hmC Level and Promotes Tumorigenesis by Activating AMPK Pathway in Papillary Thyroid Cancer

Chi

Zhang

et al. 2022

International Journal of Endocrinology

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Thyroid cancer is the most common endocrine malignant tumor. The accurate risk stratification and prognosis assessment is particularly important for patients with thyroid cancer, which can reduce the tumor recurrence rate, morbidity, and mortality effectively. DNA methylation is one of the most widely studied epigenetic modifications. Many studies have shown that 5hmC-mediated demethylation played an important role in tumors. The hydroxylation of 5mC is catalyzed by ten-eleven translocation dioxygenase (TET). In this study, we first found that the abnormal expression of 5hmC was closely related to microcarcinoma, multifocal, extraglandular invasion and lymph node metastasis of thyroid carcinoma. Then, we identified TET3 was differentially expressed in thyroid cancers and normal tissues from the TET family. TET3 can promote the proliferation, migration, and invasion of thyroid cancer. TET3-mediated 5hmC can regulate the transcription of AMPK pathway-related genes to activate the AMPK pathway and autophagy and therefore promote PTC proliferation. These findings provide a preclinical rationale for the design of novel therapeutic strategies for this target to improve the clinical outcome of patients with PTC.

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Epigenetic induction of tumor stemness via the lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma

Cited by 23 publications

References 50 publications

LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

LncRNA SNHG8 Promotes Liver Cancer Proliferation and Metastasis by Sponging miR-542-3p and miR-4701-5p

The stemness of hepatocytes is maintained by high levels of lipopolysaccharide via YAP1 activation

TET3 Mediates 5hmC Level and Promotes Tumorigenesis by Activating AMPK Pathway in Papillary Thyroid Cancer

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