1.Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance.
Yingjiao XUE ; Shenda HOU ; Hongbin JI ; Xiangkun HAN
Protein & Cell 2017;8(3):178-190
Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Carcinoma, Non-Small-Cell Lung
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genetics
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metabolism
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Drug Resistance, Neoplasm
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genetics
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Humans
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Lung Neoplasms
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genetics
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metabolism
2.Circular RNA in Lung Cancer Research: Biogenesis, Functions and Roles.
Chinese Journal of Lung Cancer 2018;21(1):50-56
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in China. In recent years, therapies for oncogenedrivers and immune checkpoints have proved inspiring. Circular RNA (circRNA), which is a kind of RNA with covalent ring structure relating to stages and metastasis of cancer, has many special biological functions in physiological processes, diseases and so on. Thus, circRNA is expected to be a potential biomarker for cancer prediction and treatment in view of its high conservation and tissue-specific. However, function analysis and regulatory mechanism of circRNA in lung cancer come so far remains unclear and limited literatures are available. In this review, we highlight the research history, formation mechanism, biological function of circRNA and research progress in cancer, especially in lung cancer. We mean to provide theoretical evidences and new ideas for researches on circRNAs in lung cancer.
Animals
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Humans
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Lung Neoplasms
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genetics
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metabolism
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RNA
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biosynthesis
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genetics
3.Specific microRNA expression profiles of lung adenocarcinoma in Xuanwei region and bioinformatic analysis for predicting their target genes and related signaling pathways.
Shuai CHEN ; Yong-Chun ZHOU ; Ying CHEN ; Xiao-Bo CHEN ; Guang-Jian LI ; Jia-Peng YANG ; Yu-Jie LEI ; Guang-Qiang ZHAO ; Qiu-Bo HUANG ; Chang-Shao YANG ; Ya-Xi DU ; Yun-Chao HUANG
Journal of Southern Medical University 2016;37(2):238-244
OBJECTIVETo identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis.
METHODSHigh-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways.
RESULTSThirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways.
CONCLUSIONThe specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.
Adenocarcinoma ; genetics ; metabolism ; Computational Biology ; Gene Expression Profiling ; Humans ; Lung ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Signal Transduction
4.FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis.
Hai Ning HONG ; Hao Nan ZHU ; Chao LI ; Chao ZANG ; Hai Wei SANG ; Li Wei CHEN ; An Sheng WANG
Journal of Southern Medical University 2022;42(8):1182-1190
OBJECTIVE:
To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance.
METHODS:
The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis.
RESULTS:
Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05).
CONCLUSION
FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
Adenocarcinoma of Lung/metabolism*
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Humans
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Kaplan-Meier Estimate
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Lung Neoplasms/metabolism*
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Neoplasm Proteins/genetics*
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Prognosis
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Proteins
5.Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma.
Wen-Qin XU ; Jing-Jing YE ; Tian-Bing CHEN
Chinese Medical Sciences Journal 2022;37(1):31-43
Objective Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis. Methods A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN. Results Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that "Cell Cycle, Mitotic" was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest. Conclusions Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD.
Adenocarcinoma of Lung/genetics*
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Humans
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Lung Neoplasms/pathology*
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MicroRNAs/metabolism*
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Prognosis
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RNA, Messenger/metabolism*
6.Research Progress of Role and Mechanism of SETD7 in Tumor Occurrence and Progression.
Chinese Journal of Lung Cancer 2023;26(1):38-45
The occurence and development of tumors is a complicated process, which not only depends on the mutation or deletion of genes, but also is affected by epigenetic regulation. Accumulating evidences have shown that epigenetic modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation, DNA damage response and tumor development. SET domain containing lysine methyltransferase 7 (SETD7) was initially identified as an important lysine methyltransferase, which methylated histone and non-histone proteins. These modifications play fundamental roles. Once this modification disorders, it can directly lead to cell abnormalities and cause many diseases. Studies have shown that SETD7 is related to the occurence and development of various tumors, but the methylation sites of SETD7 and its regulatory mechanism have not been fully elucidated. This article summarizes the research progress of the role of SETD7 on histone and non-histone methylation modification in tumors and the molecular mechanism, in order to provide new therapeutic targets for tumor pathogenesis and diagnosis.
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Humans
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Epigenesis, Genetic
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Histone-Lysine N-Methyltransferase/metabolism*
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Lysine/metabolism*
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Lung Neoplasms/genetics*
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Histones/metabolism*
7.Effects of heat shock protein 70-2 gene polymorphisms on the transcription of HSP 70-2 mRNA and the translation of HSP 70 protein in lung cancer.
Hao-quan LU ; Yu-zhen WANG ; Peng-hui SUN ; Shou-pei LIANG ; Jie LI ; Xiao-long WANG ; Dong XU ; Wu YAO ; Yi-ming WU ; Fang ZHOU
Chinese Journal of Preventive Medicine 2012;46(5):452-455
OBJECTIVEThis study aimed to investigate the effects of gene polymorphism of heat shock protein 70-2 (HSP 70-2) 1267A/G on the mRNA level HSP 70-2 mRNA and the protein level HSP 70 in human lung cancer.
METHODSForty six lung cancer patients diagnosed histopathologically between February and August 2008 from a hospital in zhengzhou were enrolled as the subjects in this study. Gene polymorphism of HSP 70-2 1276A/G in 46 patients with lung cancer was detected by PCR-RFLP. The mRNA levels of HSP 70-2 mRNA and the protein levels of HSP 70 in lung tissue and para-cancerous tissues of these subjects were determined by RT-PCR and Western blotting respectively.
RESULTSThe expression levels of HSP 70-2 mRNA (1.02 ± 0.30) and HSP 70 protein (0.44 ± 0.12) in the lung cancer tissues was significantly higher than that in para-cancerous tissues (0.19 ± 0.04, 0.12 ± 0.02). The relative levels of HSP 70-2 mRNA in the subjects with AA genotype (1.32 ± 0.22) were significantly higher than the patients with AG genotype or GG genotype (0.95 ± 0.17, 0.70 ± 0.16) at the site of 1267 (A/G) (P < 0.01); however, the relative protein levels of HSP 70 were 0.47 ± 0.13 (AA genotype), 0.42 ± 0.11 (AG genotype), 0.45 ± 0.11 (GG genotype), respectively, which showed no statistically significant difference (P > 0.05).
CONCLUSIONThe polymorphism of HSP 70-2 1267 (A/G) is highly associated with the transcription level of HSP 70-2 mRNA, but not with the expression level of HSP 70 protein.
Adenocarcinoma ; genetics ; metabolism ; pathology ; Female ; Genotype ; HSP70 Heat-Shock Proteins ; genetics ; Humans ; Lung ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; RNA, Messenger ; genetics
8.Functional prediction of KIAA0101 gene in human non-small cell lung cancer.
Hua LI ; Wen-li MA ; Chang-qing ZUO ; Shuang LIANG ; Yun YE ; Wen-ling ZHENG
Journal of Southern Medical University 2010;30(1):157-159
OBJECTIVETo predict the function of KIAA0101 gene over-expressed in human non-small cell lung cancer by bioinformatics methods.
METHODSThe gene expression profiles of the lung cancer tissues and the adjacent normal tissues were compared by dChip software analysis, and the differential genes coexpressed with KIAA0101 gene were identified. The biological functions of these genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), Gene Ontology (GO) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the common transcription factors of these genes were predicted using Gene Annotation Tool to Help Explain Relationships (GATHER).
RESULTSNine genes were found to have at least two-fold overexpressions in the lung cancer tissues in comparison with the expression level in the adjacent normal tissues, and showed similar pattern of expression variations in the lung cancer tissue. Most of these genes had the E2F1 binding sites in the promoter region.
CONCLUSIONKIAA0101 gene may participate in the cell cycle regulation of the non-small cell lung cancer, and the expression levels of the 9 genes identified may be regulated by the transcription factor E2F1.
Carcinoma, Non-Small-Cell Lung ; genetics ; Carrier Proteins ; genetics ; metabolism ; Gene Expression Profiling ; methods ; Humans ; Lung Neoplasms ; genetics
9.Detection of ROS1 gene rearrangement by FISH and analysis of its clinical features in non-small cell lung cancer patients.
Hongxia CHENG ; Lun YE ; Liquan XUE
Chinese Journal of Oncology 2014;36(10):751-754
OBJECTIVETo detect the frequency of ROS1 gene rearrangement in non-small cell lung cancer ( NSCLC) patients by FISH, and to analyze the relationship between ROS1 gene rearrangement and clinical features (including age, sex, stage, histology, smoking history) with NSCLC.
METHODSThe ROS1 gene rearrangement in histological sections of 1 652 NSCLC tissues was detected by FISH. The extracted RNA was amplified and the sequences were analyzed by Sanger sequencing for ROS1-positive samples.
RESULTSROS1 rearrangement was identified in 53 specimens (3.2%) from the 1 652 NSCLC tissues. Among these positive cases, 15 were CD74-ROS1, 13 were SLC34A2-ROS1, 13 were SDC4-ROS1 and 12 were TPM3-ROS1. The frequency of ROS1 rearrangement was significantly higher in never-smoking patients (49 cases) than in smokers (4 cases) (P < 0.05). Patients with ROS1-positive NSCLC tended to be younger and there was no significant difference in sex (P > 0.05). All of the ROS1-positive samples were adenocarcinomas, with a tendency toward higher clinical stage (P < 0.05).
CONCLUSIONSROS1 rearrangement has diversity, and may be defined as a new molecular subtype of NSCLC. ROS1 rearrangement tends to occur in younger, and never-smoker lung adenocarcinoma patients.
Adenocarcinoma ; genetics ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; genetics ; Oncogenes ; Protein-Tyrosine Kinases ; genetics ; Proto-Oncogene Proteins ; genetics ; metabolism
10.The role of DNA damage repair and Chk2 protein in hyper-radiosensitivity of lung adenocarcinoma A549 cells.
Hongge WU ; Qitian CHEN ; Yong ZHANG ; Gang WU ; Rui MENG ; Jing CHENG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2012;32(5):750-754
To explore the role of the Chk2 protein expression and DNA double strand breaks (DSBs) repair in low dose hyper-radiosensitivity (HRS)/increased radioresistance (IRR) of non-small cell lung cancer, A549 cells were subjected to irradiation at the dosage ranging from 0.05-2 Gy. Clonogenic survival was measured by using fluorescence-activated cell sorting (FACS) plating technique. Percentage of cells in M-phase after low doses of X-irradiation was evaluated by phospho-histone H3-FITC/PI and Western blotting was used to detect protein expression of Chk2 and phospo-Chk2. DNA DSBs repair efficiency was also measured by induction and persistence of γ-H2AX. The results showed that the killing ability of irradiation with A549 cells increased at low conditioning dose below 0.3 Gy. Within the dose of 0.3 to 0.5 Gy, A549 cells showed a certain extent of radiation resistance. And when the dose was more than 0.5 Gy, survival fraction exhibited a negative correlation with the dosage. There was no difference between the 0.1 or 0.2 Gy dosage groups and the un-irradiated group in terms of the percentage of cells in M phase. But in the high dosage group (0.3-1.0 Gy), the percentage of cells in M phase was decreased markedly. In addition, the percentage of cells in M phase began to decrease two hours after irradiation. One hour after irradiation, there was no conspicuous activation of Chk2 kinase in 0.1 or 0.2 Gy group, but when the irradiation dose reached 0.3 Gy or higher, Chk2 kinase started to be activated and the activation level showed no significant difference among high dosage groups (0.4, 0.5, 1.0 Gy). Within 1 to 6 h, the DNA DSBs repair efficiency was decreased at 0.2 Gy but increased at 0.5 Gy and 1.0 Gy, which was in line with Chk2 activation. We are led to conclude that the mechanism of HRS/IRR in A549 cell line was probably due to early G(2)/M checkpoint arrest and enhanced DNA DSBs repair. In this regard, Chk2 activation plays a key role in G(2)/M checkpoint activation.
Adenocarcinoma
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genetics
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metabolism
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Cell Line, Tumor
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Checkpoint Kinase 2
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genetics
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metabolism
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DNA Damage
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genetics
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DNA Repair
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genetics
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Humans
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Lung Neoplasms
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genetics
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metabolism
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Radiation Tolerance
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genetics