• Genomics & Informatics
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• 제18권4호
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• pp.36.1-36.9
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• 2020

Since lung cancer is a major causative for cancer-related deaths, the investigations for discovering biomarkers to diagnose at an early stage and to apply therapeutic strategies have been continuously conducted. Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are being exponentially studied as promising biomarkers of lung cancer. Moreover, supportive evidence provides the competing endogenous RNA (ceRNA) network between lncRNAs and miRNAs participating in lung tumorigenesis. This review introduced the oncogenic or tumor-suppressive roles of lncRNAs and miRNAs in lung cancer cells and summarized the involvement of the lncRNA/miRNA ceRNA networks in carcinogenesis and therapeutic resistance of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3751-3755
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• 2012

Aim: Tea polyphenols are known to play roles in critical steps of human lung carcinoma cell metastasis. For understanding the mechanisms whereby they inhibit tumor metastasis, the present study was conducted to investigate their effects on the adhesion of highly metastatic lung carcinoma cell lines (PG cells) to endothelial cells (EC cells) and adhesion molecule expression in vitro. Methods: The expression of CD44 or CD54 in the PG cells was detected by flow cytometry and adhesion of PG cells to EC cells was assessed by confocal microscopy double fluorescence staining. Results: The results showed that tea polyphenols: (1) inhibited the expression of CD44 and CD54, two important adhesion molecules in the PG cells in a dose-dependent manner; (2) significantly blocked the adhesion of PG cells to EC cells not only in a state of rest but also when active; and (3) influenced CD44 and CD54 expression during the adhesion process of PG cells to EC cells. Conclusions: The data indicated that the blocking role of tea polyphenols in the adhesion of PG cells to EC cells is related to CD44 and CD54. The mechanism of tea polyphenol prevention of human lung carcinoma metastasis might be through inhibiting adhesion molecule expression to block cancer cell adhesion.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4039-4044
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• 2014

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

• Genomics & Informatics
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• 제11권4호
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• pp.245-253
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• 2013

A radioresistant cell line was established by fractionated ionizing radiation (IR) and assessed by a clonogenic assay, flow cytometry, and Western blot analysis, as well as zymography and a wound healing assay. Microarray was performed to profile global expression and to search for differentially expressed genes (DEGs) in response to IR. H460R cells demonstrated increased cell scattering and acidic vesicular organelles compared with parental cells. Concomitantly, H460R cells showed characteristics of increased migration and matrix metalloproteinase activity. In addition, H460R cells were resistant to IR, exhibiting reduced expression levels of ionizing responsive proteins (p-p53 and ${\gamma}$-H2AX); apoptosis-related molecules, such as cleaved poly(ADP ribose) polymerase; and endoplasmic reticulum stress-related molecules, such as glucose-regulated protein (GRP78) and C/EBP-homologous protein compared with parental cells, whereas the expression of anti-apoptotic X-linked inhibitor of apoptosis protein was increased. Among DEGs, syntrophin beta 2 (SNTB2) significantly increased in H460R cells in response to IR. Knockdown of SNTB2 by siRNA was more sensitive than the control after IR exposure in H460, H460R, and H1299 cells. Our study suggests that H460R cells have differential properties, including cell morphology, potential for metastasis, and resistance to IR, compared with parental cells. In addition, SNTB2 may play an important role in radioresistance. H460R cells could be helpful in in vitro systems for elucidating the molecular mechanisms of and discovering drugs to overcome radioresistance in lung cancer therapy.

• Tuberculosis and Respiratory Diseases
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• 제72권4호
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• pp.343-351
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• 2012

Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. Methods: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. Results: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. Conclusion: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.

• BMB Reports
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• 제48권3호
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• pp.159-165
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• 2015

Although the short isoform of ErbB3-binding protein 1 (Ebp1), p42 has been considered to be a potent tumor suppressor in a number of human cancers, whether p42 suppresses tumorigenesis of lung cancer cells has never been clarified. In the current study we investigated the tumor suppressor role of p42 in non-small cell lung cancer cells. Our data suggest that the expression level of p42 is inversely correlated with the cancerous properties of NSCLC cells and that ectopic expression of p42 is sufficient to inhibit cell proliferation, anchorage-independent growth, and invasion as well as tumor growth in vivo. Interestingly, p42 suppresses Akt activation and overexpression of a constitutively active form of Akt restores the tumorigenic activity of A549 cells that is ablated by exogenous p42 expression. Thus, we propose that p42 Ebp1 functions as a potent tumor suppressor of NSCLC through interruption of Akt signaling.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.760-765
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• 1998

연구배경: 암세포에서 포도당의 유입이 증가되어 있다는 사실이 오래 전부터 알려져 왔고 이런 현상을 이용하여 FDG-PET 영상이 암의 진단에 이용되고 있다. 그러나, 암세포에서 포도당 유입이 증가하는 기전에 대해서는 모르고 있다. 최근, 여러 연구에서 소화기계의 악성종양과 두경부종양에서 포도당 운반체의 mRNA 의 존재가 증명되었고, 포도당 운반체가 암세포에서의 포도당 유입 증가와 관련이 있을 가능성을 시사하였다. 폐암에서도 포도당대사가 항진되어 있다. 저자등은 폐암에서의 포도당 유입이 증가하는 기전에 대해 알아 보기 위하여 사람 폐암세포주에서 포도당 mRNA의 발현여부를 확인하였다. 방 법: 15종의 사람 폐암 세포주와 불멸화시킨 기관지 상피세포주에서 total RNA를 추출하였다. $20{\mu}g$의 total RNA를 전기영동시킨후, 포도당 운반체 1형과 3 형에 대한 cDNA를 probe로 Northern blot analysis를 시행하였다. 결 과: 14종의 사람 폐암 세포주중에서 13종에서 포도당 운반체 1형의 mRNA 발현을 확인하였고, 14종의 사람 폐암 세포주중에서 10종에서 포도당 운반체 3형의 mRNA 발현을 확인하였다. 불멸화시킨 기관지 상피세포주의 포도당 운반체 1형의 mRNA 발현을 확인할 수 있었고 3형의 mRNA 발현은 확인할 수 없었다. 결 론: 폐암에서 포도당 대사의 증가는 포도당 운반체 1형과 3형의 발현과 관련이 있을 것으로 사료된다.

• 한국융합학회논문지
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• 제13권2호
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• pp.257-262
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• 2022

본 연구의 목적은 다양한 생리활성물질을 함유한 비트 추출물의 다양한 농도를 이용하여 인체 유래 암세포 증식 저해를 살펴보기 위하여 실시하였다. 실험에 사용한 인체 유래 암세포는 6종으로 전립샘암세포 DU145, 폐암세포 A549, 유방암세포 MCF-7, 자궁암세포 HeLa, 간암세포 SNU-182, 담도암세포 SNU-1196을 사용하였으며, 비트 추출물의 다양한 농도에 대한 암세포증식 저해를 CCK-8 방법으로 측정하였다. 암세포증식 저해를 살펴본 결과 비트 추출물은 전립샘암세포 DU145를 모든 농도에서 유의성있게 농도 의존적으로 저해하였으며, 폐암세포 A549, 전립샘암세포 DU-145는 100ug/mL, 1000ug/mL에서 자궁암세포 HeLa, 간암세포 SNU-182, 담도암세포 SNU-1196는 1000ug/mL에서 유의한 증식 저해를 보였다. 실험 결과, 다양한 인체 유래 암세포를 이용한 비트 추출물의 암세포증식 저해는 암 예방 효과 및 기능성 식품 개발의 가능성을 제공한다고 볼 수 있다.

• Genomics & Informatics
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• 제12권2호
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• pp.50-57
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• 2014

We present a new next-generation sequencing-based method to identify somatic mutations of lung cancer. It is a comprehensive mutation profiling protocol to detect somatic mutations in 30 genes found frequently in lung adenocarcinoma. The total length of the target regions is 107 kb, and a capture assay was designed to cover 99% of it. This method exhibited about 97% mean coverage at $30{\times}$ sequencing depth and 42% average specificity when sequencing of more than 3.25 Gb was carried out for the normal sample. We discovered 513 variations from targeted exome sequencing of lung cancer cells, which is 3.9-fold higher than in the normal sample. The variations in cancer cells included previously reported somatic mutations in the COSMIC database, such as variations in TP53, KRAS, and STK11 of sample H-23 and in EGFR of sample H-1650, especially with more than $1,000{\times}$ coverage. Among the somatic mutations, up to 91% of single nucleotide polymorphisms from the two cancer samples were validated by DNA microarray-based genotyping. Our results demonstrated the feasibility of high-throughput mutation profiling with lung adenocarcinoma samples, and the profiling method can be used as a robust and effective protocol for somatic variant screening.

• BMB Reports
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• 제54권8호
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• pp.425-430
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• 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients.