scholarly journals Long noncoding RNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 to predict poor prognosis in lung cancer patients

2020 ◽  
Author(s):  
Haihua Tian ◽  
Jinchang Pan ◽  
Shuai Fang ◽  
Chengwei Zhou ◽  
Hui Tian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Colony Formation ◽  
Poor Prognosis ◽  
Lung Cancer Cell ◽  
Lung Cancer Patients ◽  
Cancer Tissues

Abstract Background: Long noncoding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. However, the epigenetic modification of lncRNA and its cognate sense gene in lung cancer remain largely unknown.Methods: qRT-PCR and Western blot were conducted to detect the expressions of DDP10-AS1 and DPP10 expression in lung cancer cell lines and tissues. The impact of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis and in vivo tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry and xenograft animal experiment. Results: A novel antisense lncRNA, DPP10-AS1, is found to be highly expressed in cancer tissues and the upregulation of DPP10-AS1 predicts poor prognosis in lung cancer patients. Notably, DPP10-AS1 promotes lung cancer cell growth, colony formation, cell cycle progression and represses apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitates lung tumor growth via upregulation of DPP10 protein in xenograft mouse model. Importantly, DPP10-AS1 positively regulates DPP10 gene expression and they are coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 associates with DPP10 mRNA but does not enhance DPP10 mRNA stability. Hypomethylation of DPP10-AS1 and DPP10 contributes to their coordinate upregulation in lung cancer.Conclusions: These findings indicate that the upregulated antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10, and DPP10-AS1 may act as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

scholarly journals Long noncoding RNA DPP10-AS1 promotes malignant processes through epigenetically activating its cognate gene DPP10 to predict poor prognosis in lung cancer patients

2019 ◽  
Author(s):  
Haihua Tian ◽  
Jinchang Pan ◽  
Shuai Fang ◽  
Chengwei Zhou ◽  
Hui Tian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Colony Formation ◽  
Poor Prognosis ◽  
Lung Cancer Cell ◽  
Lung Cancer Patients ◽  
Cancer Tissues

Abstract Background Long noncoding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. However, the epigenetic modification of lncRNA and its cognate sense gene in lung cancer remain largely unknown.Methods : qRT-PCR and Western blot were conducted to detect the expressions of DDP10-AS1 and DPP10 expression in lung cancer cell lines and tissues. The impact of DDP10-AS1 on DPP10 expression, cell growth, invasion, apoptosis and in vivo tumor growth were investigated in lung cancer cells by Western blot, rescue experiments, colony formation, flow cytometry and xenograft animal experiment.Results A novel antisense lncRNA, DPP10-AS1, is found to be highly expressed in cancer tissues and the upregulation of DPP10-AS1 predicts poor prognosis in lung cancer patients. Notably, DPP10-AS1 promotes lung cancer cell growth, colony formation, cell cycle progression and represses apoptosis in lung cancer cells by upregulating DPP10 expression. Additionally, DPP10-AS1 facilitates lung tumor growth via upregulation of DPP10 protein in xenograft mouse model. Importantly, DPP10-AS1 positively regulates DPP10 gene expression and they are coordinately upregulated in lung cancer tissues. Mechanically, DPP10-AS1 associates with DPP10 mRNA but does not enhance DPP10 mRNA stability. Hypomethylation of DPP10-AS1 and DPP10 contributes to their coordinate upregulation in lung cancer.Conclusions These findings indicate that the upregulated antisense lncRNA DPP10-AS1 promotes lung cancer malignant processes and facilitates tumorigenesis by epigenetically regulating its cognate sense gene DPP10, and DPP10-AS1 may act as a candidate prognostic biomarker and a potential therapeutic target in lung cancer.

scholarly journals S100A2 induces the growth of Calu-6 Lung Cancer Cells via apoptosis inhibition, invasion enhancement and promoting cell division

2019 ◽  
Author(s):  
Ting Wang ◽  
Yiqian Liang ◽  
Asmitananda Thakur
Keyword(s):  
Lung Cancer ◽  
Cell Division ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Lung Cancer Cell ◽  
Lung Cancer Patients ◽  
Apoptosis Inhibition

Abstract Background S100 calcium binding protein A2 (S100A2) has been confirmed to have an abnormal expression in lung cancer and is associated with a better disease-free internal of lung cancer patients. Our previous studies on S100A2 in lung cancer concentrated on the clinical roles of this protein in lung cancer, finding that S100A2 increasingly expressed in the sera, tissues and plural effusion of lung cancer patients. This study emphasizes its value in the lung cancer cell line.Methods We constructed a S100A2 expression lentivirus vector, then transfected it and blank vector into the Calu-6 lung cancer cell line respectively. After the successful transfection, (which was confirmed by RT-PCR and Western-blot), we used MTT, transwell and flow cytometric analysis to compare the differences in cell proliferation, cell migration, cell invasion, cell apoptosis and cell cycle among the three groups (Calu-6, Calu/neo, Calu-6/S100A2).Results Calu-6 lung cancer cells showed a shift from G1 to S phase after being transfected with S100A2, compared with the control groups. Additionally, Calu-6/S1000A2 cells had enhanced abilities of invasion and down-abilities of apoptosis in contrast with the blank groups (P<0.05). However, there were no significant difference among these three group in the cell behaviors of migration and proliferation (P>0.05).Conclusion Our results firstly indicate that S100A2 has a positive influence on the biological characteristics of Calu-6 lung cancer cell line, including cell division, invasion and apoptosis inhibition. It may play a significant role in the genesis and progression of lung cancer.

Identification of Therapeutic Targets and Prognostic Biomarkers of IGF2BPs in the Lung Cancer Microenvironment

2021 ◽  
Author(s):  
Xuanzheng Wang ◽  
Weina Kong ◽  
Fan Guo ◽  
Ruocheng Sha ◽  
Gang Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Binding Proteins ◽  
Rna Binding ◽  
Therapeutic Targets ◽  
Prognostic Biomarkers ◽  
Lung Cancer Patients ◽  
Cancer Tissues

Abstract Background: Lung cancer is one of the most common malignances with an ever-increasing incidence and high mortality. The insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as RNA-binding proteins play an important role in messenger RNA (mRNA) regulation during tumor development. Even so, the expression and prognostic values of IGF2BPs in lung cancer have not been clarified.Main methods: To address this issue, the study investigated the roles of IGF2BPs in the prognosis of lung cancer by using public databases and quantitative real-time PCR (Q-PCR).Results: The transcriptional levels of IGF2BP1/2/3 in lung cancer tissues were significantly elevated, associating with pathological stages and poor prognosis of overall survival (OS) and progression-free survival (FP) in lung cancer patients. A high mutation rate of IGF2BPs (24%) was also observed of patients with lung cancer. The functions of differentially expressed IGF2BPs are primarily related to the spliceosome, hippo signaling pathway and transcriptional misregulation in cancer. Finally, we found significant correlations among the expression of IGF2BPs and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells).Conclusions: The results indicated that high mRNA expression of IGF2BP1/2/3 was found in lung cancer tissues, significantly associating with tumor grades and poor prognosis of OS and FP. Our results may provide insights for the selection of therapeutic targets and prognostic biomarkers for lung cancer patients.

scholarly journals Capilliposide C from Lysimachia capillipes Restores Radiosensitivity in Ionizing Radiation-Resistant Lung Cancer Cells Through Regulation of ERRFI1/EGFR/STAT3 Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Kan Wu ◽  
Xueqin Chen ◽  
Jianguo Feng ◽  
Shirong Zhang ◽  
Yasi Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Lung Cancer Cells ◽  
Rna Seq ◽  
Lung Cancer Cell ◽  
Lung Cancer Patients ◽  
Damage Repair

AimsRadiation therapy is used as the primary treatment for lung cancer. Unfortunately, radiation resistance remains to be the major clinic problem for lung cancer patients. Lysimachia capillipes capilliposide C (LC-C), an extract from LC Hemsl, has demonstrated multiple anti-cancer effects in several types of cancer. Here, we investigated the potential therapeutic impacts of LC-C on radiosensitivity in lung cancer cells and their underlying mechanisms.MethodsNon-small cell lung cancer cell lines were initially irradiated to generate ionizing radiation (IR)-resistant lung cancer cell lines. RNA-seq analysis was used to examine the whole-transcriptome alteration in IR-resistant lung cancer cells treated with or without LC-C, and the differentially expressed genes with most significance were verified by RT-qPCR. Colony formation assays were performed to determine the effect of LC-C and the target gene ErbB receptor feedback inhibitor 1 (ERRFI1) on radiosensitivity of IR-resistant lung cancer cells. In addition, effects of ERRFI1 on cell cycle distribution, DNA damage repair activity were assessed by flow cytometry and γ-H2AX immunofluorescence staining respectively. Western blotting was performed to identify the activation of related signaling pathways. Tumor xenograft experiments were conducted to observe the effect of LC-C and ERRFI1 on radiosensitivity of IR-resistant lung cancer cells in vivo.ResultsCompared with parental cells, IR-resistant lung cancer cells were more resistant to radiation. LC-C significantly enhanced the effect of radiation in IR-resistant lung cancer cells both in vitro and in vivo and validated ERRFI1 as a candidate downstream gene by RNA-seq. Forced expression of ERRFI1 alone could significantly increase the radiosensitivity of IR-resistant lung cancer cells, while silencing of ERRFI1 attenuated the radiosensitizing function of LC-C. Accordingly, LC-C and ERRFI1 effectively inhibited IR-induced DNA damage repair, and ERRFI1 significantly induced G2/M checkpoint arrest. Additional investigations revealed that down-regulation of EGFR/STAT3 pathway played an important role in radiosensitization between ERRFI1 and LC-C. Furthermore, the high expression level of ERRFI1 was associated with high overall survival rates in lung cancer patients.ConclusionsTreatment of LC-C may serve as a promising therapeutic strategy to overcome the radiation resistance and ERRFI1 may be a potential therapeutic target in NSCLC.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Long non-coding RNA AFAP1-AS1 accelerates lung cancer cells migration and invasion by interacting with SNIP1 to upregulate c-Myc

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu Zhong ◽  
Liting Yang ◽  
Fang Xiong ◽  
Yi He ◽  
Yanyan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Lung Cancer Patients ◽  
Lung Cancer Metastasis ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractActin filament associated protein 1 antisense RNA 1 (named AFAP1-AS1) is a long non-coding RNA and overexpressed in many cancers. This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer. The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization. The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells. To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer, we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses. AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients’ poor prognosis. In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis. AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1 (named SNIP1), which inhibited ubiquitination and degradation of c-Myc protein. Upregulation of c-Myc molecule in turn promoted the expression of ZEB1, ZEB2, and SNAIL gene, which ultimately enhanced epithelial to mesenchymal transition (EMT) and lung cancer metastasis. Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer’s migration and invasion may provide novel therapeutic targets for lung cancer patients’ early diagnosis and therapy.

Detection of circulating cancer cells in lung cancer patients with a panel of marker genes

2008 ◽  
Vol 372 (4) ◽  
pp. 756-760 ◽  
Author(s):  
Lei Liu ◽  
Guo-qing Liao ◽  
Pei He ◽  
Hong Zhu ◽  
Peng-hui Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Marker Genes ◽  
Lung Cancer Patients ◽  
Circulating Cancer Cells

scholarly journals Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Liyuan Song ◽  
Xianhui Wang ◽  
Wang Cheng ◽  
Yi Wu ◽  
Min Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Markers ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Clinicopathological Parameters ◽  
Cancer Specific Survival ◽  
Lung Cancer Patients ◽  
Favorable Prognosis

Abstract Background In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear. Methods CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan–Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein–protein interaction and gene–gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively. Results CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients. Conclusions CTSF might play an anti-tumor effect via regulating immune response of NSCLC.

Comprehensive cancer genomics-based screening of new therapeutic targets and biomarkers for lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21031-e21031
Author(s):  
Yataro Daigo ◽  
Atsushi Takano ◽  
Yusuke Nakamura
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Therapeutic Target ◽  
Cancer Genomics ◽  
Cancer Biomarkers ◽  
Lung Cancer Cells ◽  
Lung Cancers ◽  
Lung Cancer Patients ◽  
Target Molecules

e21031 Background: Since the clinical outcome of advanced lung cancer patients is still poor after standard therapies, development of new anti-cancer drugs with minimum risk of adverse effects and cancer biomarkers for precision medicine is urgently required. Methods: We have been screening new therapeutic target molecules and molecular biomarkers for lung cancers as follows; i) To identify overexpressed genes in lung cancers by the gene expression profile analysis, ii) To verify the target genes for their scarce expression in normal tissues, iii) To validate the clinicopathologic importance of their protein expression by tissue microarray covering 263 lung cancers, and iv) To confirm their function for the growth and/or invasive ability of the lung cancer cells by siRNAs and gene transfection assays. Results: We identified dozens of candidate target molecules and selected a gene encoding protein with a GAP domain, LAPG1 (lung cancer-associated protein with Gap domain 1). Immunohistochemical analysis showed that LAPG1 expression was observed in 69.9% of lung cancers. Moreover positivity of LAPG1 expression was associated with poor prognosis of lung cancer patients. Knockdown of LAPG1 expression by siRNAs suppressed growth of lung cancer cells. Introduction of LAPG1 increased the invasive activity of mammalian cells, indicating that LAPG1 could be a prognostic biomarker and therapeutic target for lung cancers. Conclusions: Comprehensive cancer genomics-based screening could be useful for selection of new cancer biomarkers and molecular targets for developing small molecules, antibodies, nucleic acid drugs, and immunotherapies.

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