scholarly journals RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases

2021 ◽  
Vol 22 (19) ◽  
pp. 10592
Author(s):  
Pai-Chi Teng ◽  
Yanwen Liang ◽  
Aliaksandr A. Yarmishyn ◽  
Yu-Jer Hsiao ◽  
Ting-Yi Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Pulmonary Diseases ◽  
Rna Modification ◽  
Rna Modifications ◽  
Mesenchymal Transition ◽  
Epigenetic Events ◽  
Development Processes ◽  
The Relationship ◽  
Related Mortality

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

scholarly journals αvβ3 Integrin induces partial EMT independent of TGF-β signaling

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yoshinobu Kariya ◽  
Midori Oyama ◽  
Takato Suzuki ◽  
Yukiko Kariya
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Αvβ3 Integrin ◽  
Poor Survival ◽  
Mesenchymal Transition ◽  
Intermediate States ◽  
Tgf Β1

AbstractEpithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.

scholarly journals ID1 mediates resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer through epithelial–mesenchymal transition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kejun Liu ◽  
Xianwen Chen ◽  
Ligang Wu ◽  
Shiyuan Chen ◽  
Nianxin Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Egfr T790m ◽  
E Cadherin

Abstract Background ID1 is associated with resistance to the first generation of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, the effect of ID1 expression on osimertinib resistance in EGFR T790M-positive NSCLC is not clear. Methods We established a drug-resistant cell line, H1975/OR, from the osimertinib-sensitive cell line H1975. Alterations in ID1 protein expression and Epithelial–mesenchymal transition (EMT)-related proteins were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA levels. ID1 silencing and overexpression were used to investigate the effects of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess the proliferation rate in cells with altered of ID1 expression. Transwell assay was used to evaluate the invasion ability of different cells. The effects on the cell cycle and apoptosis were also compared using flow cytometry. Results In our study, we found that in osimertinib-resistant NSCLC cells, the expression level of the EMT-related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin were higher than those of sensitive cells. ID1 expression levels was closely related to E-cadherin and vimentin in both osimertinib-sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression in H1975/OR cells could inhibit cell proliferation, reduce cell invasion, promote cell apoptosis and arrested the cell cycle in the G1/G0 stage phase. Our study suggests that ID1 may induce EMT in EGFR T790M-positive NSCLC, which mediates drug resistance of osimertinib. Conclusions Our study revealed the mechanism of ID1 mediated resistance to osimertinib in EGFR T790M-positive NSCLC through EMT, which may provide new ideas and methods for the treatment of EGFR mutated NSCLC after osimertinib resistance.

scholarly journals ARHGAP10 inhibits the epithelial–mesenchymal transition of non-small cell lung cancer by inactivating PI3K/Akt/GSK3β signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lan-Lan Lin ◽  
Fan Yang ◽  
Dong-Huan Zhang ◽  
Cong Hu ◽  
Sheng Yang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Rho Gtpase ◽  
Epithelial Mesenchymal Transition ◽  
Essential Element ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Abstract Background Rho GTPase activating protein 10 (ARHGAP10) has been implicated as an essential element in multiple cellular process, including cell migration, adhesion and actin cytoskeleton dynamic reorganization. However, the correlation of ARHGAP10 expression with epithelial–mesenchymal transition (EMT) in lung cancer cells is unclear and remains to be elucidated. Herein, we investigated the relationship between the trait of ARHGAP10 and non-small cell lung cancer (NSCLC) pathological process. Methods Immunohistochemistry was conducted to evaluate the expression of ARHGAP10 in NSCLC tissues. CCK-8 assays, Transwell assays, scratch assays were applied to assess cell proliferation, invasion and migration. The expression levels of EMT biomarkers and active molecules involved in PI3K/Akt/GSK3β signaling pathway were examined through immunofluorescence and Western blot. Results ARHGAP10 was detected to be lower expression in NSCLC tissues compared with normal tissues from individuals. Moreover, overexpression of ARHGAP10 inhibited migratory and invasive potentials of A549 and NCI-H1299 cells. In addition, ARHGAP10 directly mediated the process of EMT via PI3K/Akt/GSK3β pathway. Meanwhile, activation of the signaling pathway of insulin-like growth factors-1 (IGF-1) reversed ARHGAP10 overexpression regulated EMT in NSCLC cells. Conclusion ARHGAP10 inhibits the epithelial–mesenchymal transition in NSCLC via PI3K/Akt/GSK3β signaling pathway, suggesting agonist of ARHGAP10 may be an optional remedy for NSCLC patients than traditional opioids.

scholarly journals MYC-targeted WDR4 promotes proliferation, metastasis, and sorafenib resistance by inducing CCNB1 translation in hepatocellular carcinoma

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Xia ◽  
Hao Zhang ◽  
Kequan Xu ◽  
Xiang Jiang ◽  
Meng Gao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
P53 Protein ◽  
Rna Modifications ◽  
M Cell ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Repeat Domain ◽  
Cell Cycle Transition

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

scholarly journals Epithelial-mesenchymal transition-associated secretory phenotype predicts survival in lung cancer patients

2014 ◽  
Vol 35 (6) ◽  
pp. 1292-1300 ◽  
Author(s):  
A. K. Reka ◽  
G. Chen ◽  
R. C. Jones ◽  
R. Amunugama ◽  
S. Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Secretory Phenotype
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