Epigenetic inactivation of LHX6 mediated microcystin-LR induced hepatocarcinogenesis via the Wnt/β-catenin and P53 signaling pathways

Chen, Hongqiang; Zhao, Ji; Li, Yan; Huang, Yujing; Chen, Dong-jiao; He, Liang-Ying; Wang, Lingqiao; Zheng, Chuanfen; Wang, Jia; Cao, Jia; Shu, Weiqun; Liu, Jinyi; Liu, Wenbin

doi:10.1016/j.envpol.2019.05.049

Cited by 32 publications

(23 citation statements)

References 34 publications

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“…Our study for the first time investigated the CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma. Chen et al [21] demonstrated that LHX6 can inhibit the proliferation, invasion and migration P53 signaling pathways during hepatocarcinogenesis. Qin et al [22] found that P53-stabilizing and activating RNA can strengthen the interaction between hnRNP K and P53, which ultimately leads to the accumulation and transactivation of P53.…”

Section: Discussionmentioning

confidence: 99%

High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining

Wu¹,

Yang²

2020

Cancer Cell Int

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Background: Hepatocellular carcinoma (HCC) is a high mortality disease, the fifth most general cancer worldwide, and the second leading to cancer-related deaths, with more than 500,000 new patients diagnosed each year. First, the high expression of centromere M (CENPM) in mammary gland tissue of b-catenin transformed mice was identified. Materials and methods: In our study, we evaluated the expression of CENPM in hepatocellular carcinoma based on data obtained from an online database. Multivariate analysis showed that the expression of CENPM and M classification was an independent prognostic factor for patients with hepatocellular carcinoma. Results: Survival analysis showed that patients with high CENPM had a worse prognosis than patients with low CENPM (P < 0.01). A multivariate Cox regression hazard model showed that B cells, CD8+ T cells, macrophages, and dendritic cells infiltrated by immune cells were statistically significant in liver cancer (P < 0.05). Using the network, the 50 most frequently changed neighbor genes of CENPM were shown, and the most common change was RAD21 (18.3%). Conclusion: Our study found that the expression of CENPM was significantly increased in patients with hepatocellular carcinoma, and it was related to a variety of clinical characteristics, its correlation with the level of immune infiltration and poor prognosis, so CENPM can be used as a useful prognosis for patients' markers and HCC.

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Section: Discussionmentioning

confidence: 99%

High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining

Wu¹,

Yang²

2020

Cancer Cell Int

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“…For gene knockdown, TET1 shRNAs and a negative control shRNA were designed and synthesized, and then subcloned into shRNA-GFP vector. Cell transfection was performed as previously described [22]. Brie y, cells were seeded in plats and cultured for 24 hours.…”

Section: Cell Transfection Experimentsmentioning

confidence: 99%

“…Soft agar assay was performed as previously described [22]. Brie y, the lower layer agar and the upper layer agar were prepared in a 24-well plate.…”

Section: Soft Agar Assaymentioning

confidence: 99%

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis

Chen

et al. 2021

Environmental Pollution

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“…Transcription factors play an important role in the malignant tumor growth, preferentially through ERN1 (endoplasmic reticulum to nucleus signaling 1) signaling pathway of endoplasmic reticulum stress (Minchenko et al 2015b, c;Tsymbal et al 2016a). The homeobox proteins represent an important group of transcription factors, which are related to tumorigenesis and has been largely investigated (Kataoka et al 2001;Guca et al 2018;Le Magnen et al 2018;Miyashita et al 2018;Chen et al 2019;Hamaidi et al 2019;Li et al 2019;Wang et al 2019). Recently, it was shown that transcriptional inhibitor ZEB2 (zinc finger E-box binding homeobox 2) functions as oncogene in human laryngeal squamous cell carcinoma (Li et al 2019).…”

mentioning

confidence: 99%

“…The encoded protein has tandem LIM domains as well as a DNA-binding homeodomain. Recently, it was shown that transcription factor LHX6 is tumor suppressor and its expression is regulated by DNA methylation and can inhibit the proliferation, invasion and migration through WNT/beta-catenin and TP53 signaling pathways during the Microcystin-LRinduced hepatocarcinogenesis (Nathalia et al 2018;Chen et al 2019). Furthermore, miR-1290 promotes proliferation, migration, and invasion of glioma cells by inhibiting LHX6, while LHX6 overexpression inhibited tumor growth (Yan et al 2018).…”

mentioning

confidence: 99%

ERN1 knockdown modifies the effect of glucose deprivation on homeobox gene expressions in U87 glioma cells

Tsymbal

Minchenko

Khita

et al. 2020

Endocrine Regulations

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Objective. The aim of the present investigation was to study the expression of genes encoding homeobox proteins ZEB2 (zinc finger E-box binding homeobox 2), TGIF1 (TGFB induced factor homeobox 1), SPAG4 (sperm associated antigen 4), LHX1 (LIM homeobox 1), LHX2, LHX6, NKX3-1 (NK3 homeobox 1), and PRRX1 (paired related homeobox 1) in U87 glioma cells in response to glucose deprivation in control glioma cells and cells with knockdown of ERN1 (endoplasmic reticulum to nucleus signaling 1), the major pathway of the endoplasmic reticulum stress signaling, for evaluation of it possible significance in the control of glioma growth through ERN1 signaling and chemoresistance.Methods. The expression level of homeobox family genes was studied in control (transfected by vector) and ERN1 knockdown U87 glioma cells under glucose deprivation condition by real-time quantitative polymerase chain reaction.Results. It was shown that the expression level of ZEB2, TGIF1, PRRX1, and LHX6 genes was up-regulated in control glioma cells treated by glucose deprivation. At the same time, the expression level of three other genes (NKX3-1, LHX1, and LHX2) was down-regulated. Furthermore, ERN1 knockdown of glioma cells significantly modified the effect glucose deprivation condition on the expression almost all studied genes. Thus, treatment of glioma cells without ERN1 enzymatic activity by glucose deprivation condition lead to down-regulation of the expression level of ZEB2 and SPAG4 as well as to more significant up-regulation of PRRX1 and TGIF1 genes. Moreover, the expression of LHX6 and NKX3-1 genes lost their sensitivity to glucose deprivation but LHX1 and LHX2 genes did not change it significantly.Conclusions. The results of this investigation demonstrate that ERN1 knockdown significantly modifies the sensitivity of most studied homeobox gene expressions to glucose deprivation condition and that these changes are a result of complex interaction of variable endoplasmic reticulum stress related and unrelated regulatory factors and contributed to glioma cell growth and possibly to their chemoresistance.

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Epigenetic inactivation of LHX6 mediated microcystin-LR induced hepatocarcinogenesis via the Wnt/β-catenin and P53 signaling pathways

Cited by 32 publications

References 34 publications

High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining

High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining

Epigenetic silencing of TET1 mediated hydroxymethylation of base excision repair pathway during lung carcinogenesis

ERN1 knockdown modifies the effect of glucose deprivation on homeobox gene expressions in U87 glioma cells

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