Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China

Wang, Juan; Duan, Yong; Meng, Qinghe; Gong, Rong; Guo, Chong; Zhao, Ying; Zhang, Yanliang

doi:10.1371/journal.pone.0203155

Cited by 20 publications

(17 citation statements)

References 38 publications

(52 reference statements)

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“…In esophageal stem cells, FZD10 expression is high, suggesting FZD10 may play a role in esophageal tumor initiation [ 135 ]. In contrast to most other studies, one study of genome-wide methylation in lung cancer found that FZD10 is hypermethylated and downregulated in tumors compared to normal tissue and FZD10 has low expression in medulloblastomas compared to normal cerebellum [ 107 , 136 ].The presence of FZD10 expression in early lesions of multiple cancers but lack of expression in normal adult tissues highlight a key characteristic of chemoprevention targets. Combined with its likely role in EMT process, this makes FZD10 a favorable drug target for prevention.…”

Section: Frizzleds In Cancer Emtmentioning

confidence: 99%

Cancer chemoprevention through Frizzled receptors and EMT

et al. 2021

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Frizzled (FZD) transmembrane receptors are well known for their role in β-catenin signaling and development and now understanding of their role in the context of cancer is growing. FZDs are often associated with the process of epithelial to mesenchymal transition (EMT) through β-catenin, but some also influence EMT through non-canonical pathways. With ten different FZDs, there is a wide range of activity from oncogenic to tumor suppressive depending on the tissue context. Alterations in FZD signaling can occur during development of premalignant lesions, supporting their potential as targets of chemoprevention agents. Agonizing or antagonizing FZD activity may affect EMT, which is a key process in lesion progression often targeted by chemoprevention agents. Recent studies identified a specific FZD as important for activity of an EMT inhibiting chemopreventive agent and other studies have highlighted the previously unrecognized potential for targeting small molecules to FZD receptors. This work demonstrates the value of investigating FZDs in chemoprevention and here we provide a review of FZDs in cancer EMT and their potential as chemoprevention targets.

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Section: Frizzleds In Cancer Emtmentioning

confidence: 99%

Cancer chemoprevention through Frizzled receptors and EMT

et al. 2021

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“…These findings suggested that air pollution-related genes might be critical in Xuanwei lung cancer progression. Numerous studies were done to elucidate the multiple mechanisms of Xuanwei and Gejiu lung cancer; however, there were currently no effective treatments for those local lung cancer patients, and the precise molecular mechanism involved remained largely unclear ( 9 , 13 , 49 , 51 – 54 ). Previous findings confirmed that microRNAs play critical roles in the development of Xuanwei and Gejiu lung cancer and might be diagnostic biomarkers ( 9 , 13 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan

et al. 2021

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The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases.

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“…Therefore, the present study focused on Xuanwei lung cancer for its regional specificity. This disease has attracted attention worldwide and a number of studies have been performed on reducing the incidence and mortality of Xuanwei lung cancer (5)(6)(7)10,59). However, the survival rate remains low and the precise mechanisms of lung cancer progression in Xuanwei county remain to be elucidated (2,60).…”

Section: Discussionmentioning

confidence: 99%

“…Third, the age of onset of lung cancer in Xuanwei has been reported to be 15-25 years younger than that of places with high incidences of lung cancer, such as Shanghai (4). lung cancer epidemiology demonstrated family aggregation and indicated that genetic variation might serve an important role in Xuanwei lung cancer tumorigenesis and progression (5)(6)(7). However, there were few studies on genes unique in Xuanwei lung cancer tumorigenesis and progression.…”

Section: Introductionmentioning

confidence: 99%

Effects and mechanism of microRNA‑218 against lung cancer

et al. 2020

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lung cancer is the most prevalent and observed type of cancer in Xuanwei county, Yunnan, South china. lung cancer in this area is called Xuanwei lung cancer. However, its pathogenesis remains largely unknown. To date, a number of studies have shown that microrna (mir)-218 functions as a tumor suppressor in multiple types of cancer. However, the role of mir-218 and its regulatory gene network in Xuanwei lung cancer have yet to be investigated. The current study identified that the expression levels of mir-218 in XWlc-05 cells were markedly lower compared with those in immortalized lung epithelial BeaS-2B cells. The present study also demonstrated that overexpression of mir-218 could decrease cell proliferation, invasion, viability and migration in Xuanwei lung cancer cell line XWlc-05 and nSclc cell line nci-H157. additionally, the results revealed that overexpression of mir-218 could induce XWlc-05 and nci-H157 cell apoptosis by arresting the cell cycle at G2/M phase. Finally, the present study demonstrated that overexpression of mir-218 could lead to a significant increase in phosphatase and tensin homolog (PTEN) and YY1 transcription factor (YY1), and a decrease in B-cell lymphoma 2 (BCL-2) and BMi1 proto-oncogene, polycomb ring finger (BMI-1) at the mrna and protein level in XWlc-05 and nci-H157 cell lines. However, we did not observe any remarkable difference in the roles of mir-218 and mir-218-mediated regulation of BCL-2, BMI-1, PTEN and YY1 expression in the progression of Xuanwei lung cancer. in conclusion, mir-218 could simultaneously suppress cell proliferation and tumor invasiveness and induce cell apoptosis by increasing PTEN and YY1 expression, while decreasing BCL-2 and BMI-1 in Xuanwei lung cancer. The results demonstrated that mir-218 might serve a vital role in tumorigenesis and progression of Xuanwei lung cancer and overexpression of mir-218 may be a novel approach for the treatment of Xuanwei lung cancer.

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Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China

Cited by 20 publications

References 38 publications

Cancer chemoprevention through Frizzled receptors and EMT

Cancer chemoprevention through Frizzled receptors and EMT

The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan

Effects and mechanism of microRNA‑218 against lung cancer

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