Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

[Advances in Long Non-coding RNAs on Resistant to EGFR-TKIs ?in Non-small Cell Lung Cancer].

ABSTRACT: Most non-small cell lung cancer patients with active epidermal growth factor receptor (EGFR) mutation will eventually acquire drug resistant to EGFR tyrosine kinase inhibitors, such as gefitinib, resulting in disease progression, which involves a variety of complex mechanisms. Up to now, the molecular mechanisms of long non-coding RNAs mediated EGFR-TKIs resistance remains poorly understood. This review aims to outline the current state of information on lncRNAs and progress on its role in EGFR-TKIs resistance in non-small cell lung cancer.

SUBMITTER: Li S

PROVIDER: S-EPMC5973017 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

[Advances in Long Non-coding RNAs on Resistant to EGFR-TKIs  in Non-small Cell Lung Cancer].

Li Shubin S Yu Hong H Zhang Gengyue G

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20180201 2

Most non-small cell lung cancer patients with active epidermal growth factor receptor (EGFR) mutation will eventually acquire drug resistant to EGFR tyrosine kinase inhibitors, such as gefitinib, resulting in disease progression, which involves a variety of complex mechanisms. Up to now, the molecular mechanisms of long non-coding RNAs mediated EGFR-TKIs resistance remains poorly understood. This review aims to outline the current state of information on lncRNAs and progress on its role in EGFR- ...[more]

PMID: 29526180

Similar Datasets

Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer.

Project description:The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR-TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs. 8.5 months, P < 0.01] in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs. 12.0 months, P = 0.778), but in patients with non-T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1-expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1, although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR-TKIs was from the subgroup with non-T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway and EMT.

| S-EPMC4695138 | biostudies-literature

Advances with Long Non-Coding RNAs in Diabetic Peripheral Neuropathy.

Project description:Long non-coding RNAs (?lncRNAs) ?are a group of non-coding RNAs longer than 200 nucleotides, which are defined as transcripts. The lncRNAs are involved in regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels. Recent studies have found that lncRNA is closely related to many diseases like neurological diseases, endocrine and metabolic disorders. Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. In this review, we highlight the latest research related to lncRNAs in DPN.

| S-EPMC7201007 | biostudies-literature

Comprehensive analysis of differentially expressed long non-coding RNAs in non-small cell lung cancer.

Project description:Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer. Long non-coding RNAs (lncRNAs) have been reported to serve prominent roles in cancer progression. However, the expression patterns and potential roles of lncRNAs in NSCLC remain to be elucidated. In the present study, four public datasets were analyzed to identify differentially expressed lncRNAs (DElncs) in NSCLC. A further dataset, GSE19188, was analyzed to validate the findings. A total of 38 upregulated and 31 downregulated lncRNAs were identified in NSCLC, compared with samples from healthy controls. Among these, 12 lncRNAs were associated with the progression of NSCLC, and dysregulated between high grade (stage III and IV) and low grade (stage II) NSCLC samples. Moreover, dysregulation of lncRNA-SIGLEC17P, GGTA1P, A2M-AS1, LINC00938, GVINP1, LINC00667 and TMPO-AS1 was associated with overall survival time in patients with NSCLC. Co-expression analyses, combined with the construction of protein-protein interaction networks, were performed to reveal the potential roles of key lncRNAs in NSCLC. The present study revealed a series of lncRNAs involved in the progression of NSCLS, which may serve as novel biomarkers for the disease.

| S-EPMC6607379 | biostudies-literature

Exosomal Long Non-Coding RNAs in Lung Diseases.

Project description:Within the non-coding genome landscape, long non-coding RNAs (lncRNAs) and their secretion within exosomes are a window that could further explain the regulation, the sustaining, and the spread of lung diseases. We present here a compilation of the current knowledge on lncRNAs commonly found in Chronic Obstructive Pulmonary Disease (COPD), asthma, Idiopathic Pulmonary Fibrosis (IPF), or lung cancers. We built interaction networks describing the mechanisms of action for COPD, asthma, and IPF, as well as private networks for H19, MALAT1, MEG3, FENDRR, CDKN2B-AS1, TUG1, HOTAIR, and GAS5 lncRNAs in lung cancers. We identified five signaling pathways targeted by these eight lncRNAs over the lung diseases mentioned above. These lncRNAs were involved in ten treatment resistances in lung cancers, with HOTAIR being itself described in seven resistances. Besides, five of them were previously described as promising biomarkers for the diagnosis and prognosis of asthma, COPD, and lung cancers. Additionally, we describe the exosomal-based studies on H19, MALAT1, HOTAIR, GAS5, UCA1, lnc-MMP2-2, GAPLINC, TBILA, AGAP2-AS1, and SOX2-OT. This review concludes on the need for additional studies describing the lncRNA mechanisms of action and confirming their potential as biomarkers, as well as their involvement in resistance to treatment, especially in non-cancerous lung diseases.

| S-EPMC7279016 | biostudies-literature

[A Review of EGFR-TKIs Therapy of Non-small Cell Lung Cancer?with Uncommon EGFR Mutations].

Project description:Lung cancer is the most common cancer and the leading cause of cancer death. Non-small cell lung cancer (NSCLC) represents over 85% of all lung cancers, and up to 50% of Asian NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations. A number of studies have consistently demonstrated that uncommon EGFR-mutated NSCLC patients treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve better survival outcomes. However, because uncommon EGFR mutations are generally associated with reduced sensitivity to EGFR-TKIs, which will bring a negative impact on the result of the study, the majority of clinical trials investigating the efficacy of EGFR-TKIs have included only patients with common EGFR mutations. In addition, uncommon EGFR mutations are rare in themselves, leading to the small number of such patients enrolled in these trials. Due to the small number and highly heterogeneous sensitivity of uncommon EGFR mutations, the efficacy of EGFR-TKIs in patients harboring uncommon EGFR mutations remains elusive. This article reviews the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations, and give some reasonable advice about the selection of treatments for patients with NSCLC who harbor uncommon EGFR mutations.

| S-EPMC6754574 | biostudies-literature

Long non-coding RNA BC087858 induces non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT in non-small-cell lung cancer.

Project description:Our previous study demonstrated that long non-coding RNA (lncRNA) BC087858 could stimulate acquired resistance to EGFR-TKIs in non-small cell lung (NSCLC) but the specific regulatory mechanism remained unknown. We aimed to explore the role and mechanism of lncRNA BC087858 on EGFR-TKIs acquired resistance. LncRNA BC087858 mRNA expression was detected by reverse transcription polymerase chain reaction in different NSCLC cell lines and tissues. The relationship between BC087858 expression and clinicopathological factors was performed by Cox multivariate regression analysis. Small-interfering RNA, flow cytometry and trans-well assay were conducted to explore the biological functions of BC087858. Western blotting was used to analyze the target proteins expression. Over-expression was observed in NSCLC cells and patients with acquired resistance to EGFR-TKIs and significantly associated with a shorter progression-free survival (PFS) (12.0 vs. 17.0 months, P = 0.0217) in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (median PFS 17.6 vs. 12.5 months, P = 0.522) but in patients with non-T790M (median PFS 8.0 vs. 18.25 months,P = 0.0427). Down-regulation of BC087858 could significantly promote PC9/R and PC9/G2 cells invasion (P < 0.05; respectively). BC087858 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the PI3K/AKT and MEK/ERK pathways and epithelial-mesenchymal transition (EMT) via up- regulating ZEB1 and Snail. In conclusion, LncRNA BC087858 could promote cells invasion and induce non-T790M mutation acquired resistance to EGFR-TKIs by activating PI3K/AKT and MEK/ERK pathways and EMT via up- regulating ZEB1 and Snail in NSCLC.

| S-EPMC5226560 | biostudies-literature

Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non-Small Cell Lung Cancer.

Project description:PurposeEpidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non-small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.Materials and methodsWe identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening.ResultsIn cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs.ConclusionOur study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

| S-EPMC8756122 | biostudies-literature

S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.

Project description:The development of resistance to EGFR Tyrosine kinase inhibitors (TKIs) in NSCLC with activating EGFR mutations is a critical limitation of this therapy. In addition to genetic alterations such as EGFR secondary mutation causing EGFR-TKI resistance, compensatory activation of signaling pathways without interruption of genome integrity remains to be defined. In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. Taken together, we present evidence for the reversal of resistance to EGFR TKI by the addition of small molecule S6K1/MDM2 antagonists that could have clinical benefit.

| S-EPMC7718330 | biostudies-literature

Expression of long non-coding RNAs (lncRNAs) has been dysregulated in non-small cell lung cancer tissues.

Project description:BackgroundNon-small cell lung cancer (NSCLC) as the most frequent type of lung cancer is associated with extensive mortality. Researchers have studied the suitability of several molecules as biomarkers for early detection of this cancer. Long non-coding RNAs (lncRNAs) as the main regulators of gene expression have also been assessed in this regard.MethodsIn the present study, we compared expression level of Fas-antisense 1 (FAS-AS1), Growth Arrest Specific 5 (GAS5), PVT1, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), taurine upregulated gene 1 (TUG1) and TNFα and hnRNPL related immunoregulatory LincRNA (THRIL) in 32 NSCLC samples and their corresponding adjacent non-cancerous tissues (ANCTs).ResultsNEAT1 has been significantly over-expressed in NSCLC tissues obtained from male subjects compared with the corresponding ANCTs (Relative expression (REx) = 3.022, P = 0.019) but not in female subjects (P = 0.975). FAS-AS1 was significantly down-regulated in NSCLC tissues obtained from both males and females subjects compared with the corresponding ANCTs (REx = - 4.12 and - 3.14, P = 0.015 and 0.033 respectively). TUG1, GAS5, THRIL and HOTAIRM1 were significantly down-regulated in tumoral tissues obtained from male subjects compared with the corresponding ANCTs.ConclusionsThe observed dysregulation of these lncRNAs in NSCLC tissues compared with the corresponding ANCTs warrants future studies to confirm the results of the current study in larger sample sizes to elaborate their role as cancer biomarkers.

| S-EPMC6417110 | biostudies-literature

EGFR-plasma mutations in prognosis for non-small cell lung cancer treated with EGFR TKIs: A meta-analysis.

Project description:BackgroundThe plasma-based epidermal growth factor receptor (EGFR) mutation testing is approved recently to use in clinical practice. However, it has not been used as a prognostic marker yet because of contradictory results.AimThis meta-analysis aims to clarify the role of the EGFR-plasma test in prognosis for non-small cell lung cancer (NSCLC) who have mutant tumors and receive EGFR tyrosine kinase inhibitors (TKIs).Methods and resultsThe PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases were searched for relevant studies by April 10, 2021. The hazard ratio (HR) from reports was extracted and used to assess the correlation of EGFR-plasma status with progression-free survival (PFS) and overall survival (OS). A total of 35 eligible studies with 4106 patients were enrolled in the final analysis. Patients with concurrent EGFR mutations in pretreatment plasma have shorter PFS (HR = 2.00, 95% confidence interval [CI]: 1.73-2.31, p < .001) and OS time (HR = 2.31, 95% CI: 1.89-2.83, p < .001) compared to the tumor-only mutation cases. Besides, the persistence of EGFR-activating mutations in post-treatment plasma is associated with worse PFS (HR = 3.84, 95% CI: 2.96-4.99, p < .001) and OS outcome (HR = 3.22, 95% CI: 2.35-4.42, p < .001) compared to others. Notably, the prognostic value of the EGFR-plasma test is also validated in treatment with third-generation EGFR TKI and significance regardless of different detection methods.ConclusionThe presence of EGFR-plasma mutations at pretreatment and after EGFR TKI initiation is the worse prognostic factor for PFS and OS in NSCLC.

| S-EPMC9351650 | biostudies-literature