3 research outputs found
Involvement of lncRNA in cancer diagnosis and prognosis and clinical implications
Full text linkLong non-coding ribonucleic acids (lncRNAs) form a subclass of non-coding RNAs (ncRNAs), they are quite long and as their name non-coding suggests they do not have a role in protein coding. lncRNAs are vital in all the key steps of tumorigenesis, such as epithelial-mesenchymal transition, cancer stem cells formation, invasion, migration, and formation of the tumor vasculature. lncRNAs are classified into oncogenic or anti-tumor lncRNAs based on their functions. Moreover, cancer stem cells show an extremely specific pattern of expression of lncRNAs, which can be used for early detection of cancer. Similarly, their pre-treatment expression levels correlate with prognosis as they participate in key tumor biology processes like metastasis and recurrence. This chapter seeks to explore both the association between lncRNA genes and cancer and the role of lncRNAs in cancer initiation and progression. Future questions would focus on what the accepted normal ranges of lncRNA expression will be, where they are present in body fluids, which could help with non-invasive tests. But for now, one thing is clear that lncRNAs could pave the way for novel cancer therapies
hsa-let-7b-5p/TMPO-AS1-mediated ceRNA networks are linked to poor prognosis for lung cancer patients with FOXM1/MAD2L1 axis
No full textAbstract Objectives MAD2L1, a spindle assembly checkpoint molecule, is associated in cancer cell proliferation and carcinogenesis, although its ceRNA network is unknown. Methods Initially, patient’s survivability associated with the gene expression was analysed by using the Kaplan–Meier plotter database. Here, we used several TCGA databases such as UALCAN, OncoDB, ENCORI, lung cancer explorer, GEPIA2, TCGAnalyzer, and CancerMIRNome to identify differential mRNA, miRNA, and lncRNA expression. The Enrichr database was utilized to identify the transcription factor regulating MAD2L1, which was then correlated with miRNA and lncRNA, forming the ceRNA network using the miRNet database. Database miRWalk and RNA22v2 were used to predict the folding energy and binding affinity between the MAD2L1 and miRNA. TIMER and TIMER 2.0 databases were incorporated to analyse the tumor infiltrating immune cells in LUAD. Results The study found that overexpression of MAD2L1 in lung cancer patients is a high-risk factor for lung adenocarcinoma (LUAD) (HR = 1.34, P = 0.001), particularly in smoker females (HR = 1.61, P = 0.018). The study revealed MAD2L1 overexpression in LUAD cases, with a fold change of 8.7, and a strong positive correlation between RNA and protein expression levels by Cancer Proteome (R = 0.764). The study identified regulatory molecules of MAD2L1 such as transcription factor FOXM1 (R = 0.770), and lncRNA TMPO-AS1 (R = 0.565) as positively correlated with MAD2L1, while miRNA hsa-let-7b-5p, negatively correlated with MAD2L1 (R = − 0.314), FOXM1 (R = − 0.393), and TMPO-AS1 (R = − 0.277). The study suggests that TMPO-AS1 suppresses tumor suppression activity of let-7b-5p and targeting hsa-let-7b-5p could regulate MAD2L1, FOXM1 and lncRNA expression levels in LUAD. Additionally, a strong folding and binding energy was identified between the MAD2L1 gene and hsa-let-7b-5p. After analyzing the tumor microenvironment, we found that CD4+ T cells and B cells negatively correlate with the overexpression of MAD2L1. Conclusion The study indicates that MAD2L1 is overexpressed in females with LUAD, highlighting its potential as a molecular classifier and prognostic biomarker, and introduces a novel regulatory ceRNA network. Graphical Abstrac
Long noncoding RNA TMPO-AS1 upregulates chromosomal passenger complex expression to promote cell proliferation in lung cancer via sponging microRNA let-7b-5p
No full textAbstract Objective This study aims to develop a ceRNA network associated with the chromosomal passenger complex (CPC) and identify a prognostic signature in lung cancer, the most diagnosed globally, to better understand the molecular mechanisms underlying tumor progression. Methods The study used R packages and publicly available databases to conduct multi-omics In-silico analyses on CPC. These tools facilitated gene expression profiling, prognostic assessment, exploration of miRNA (microRNA), lncRNA (long non-coding RNA), transcription factor interactions, and pathway enrichment analysis. Molecular docking tools were used to evaluate binding affinities of CPC proteins with tobacco carcinogens, selective Aurora kinase B inhibitors, FDA-approved chemotherapeutics, and natural compounds. Immune landscape analysis was conducted using the SPRING viewer to visualize immune cell subpopulations in NSCLC, validated by correlation analysis using the GSCA database. Results The study reveals that CPC genes—BIRC5, CDCA8, INCENP, and AURKB—are overexpressed in lung adenocarcinoma (LUAD) and are associated with poor overall survival, especially in smokers. A dysregulated ceRNA axis involving lncRNA TMPO-AS1 and miRNA-hsa-let-7b-5p was identified, along with transcription factor E2F1, which shows a strong correlation with the CPC genes. Notably, TMPO-AS1 and E2F1 are positively correlated, while hsa-let-7b-5p is negatively correlated with the CPCs, contributing to tumor progression. Downregulation of hsa-let-7b-5p is linked to poorer outcomes, highlighting its potential as a therapeutic target. Nicotine and NNK show stable binding, suggesting potential roles in activating the CPC pathway and contributing to LUAD progression. CPCs have a strong binding affinity with Hesperidin, a natural bioflavonoid, compared to known chemotherapeutic agents like docetaxel and paclitaxel. CPC genes are negatively correlated with CD4⁺ T cells, indicating a role in promoting an immunosuppressive tumor microenvironment. Conclusion Lung adenocarcinoma patients have poorer prognosis due to higher levels of CPCs, TMPO-AS1, and E2F1. A sponge complex between TMPO-AS1 and hsa-let-7b-5p may contribute to the tumor progression, and targeting CPCs with natural compounds could offer therapeutic potential. Highlights 1. The overexpression of chromosomal passenger complex genes, AURKB, BIRC5, CDCA8, and INCENP is significantly associated with poor prognosis in lung adenocarcinoma (LUAD), particularly among smokers. 2. The competing endogenous RNA (ceRNA) axis, which involves the long non-coding RNA TMPO-AS1 and the miRNA hsa-let-7b-5p, regulates the expression of these CPC genes. TMPO-AS1 shows a positive correlation with CPC genes, while hsa-let-7b-5p shows a negative correlation. 3. Survival analysis indicates that the combined expression of CPC genes, TMPO-AS1, hsa-let-7b-5p, and E2F1 may serve as a reliable prognostic biomarker panel for LUAD in smokers. 4. Hesperidin exhibits a strong binding affinity to CPC proteins, particularly AURKB, when compared to Barasertib, Docetaxel, and Paclitaxel, highlighting its potential as a therapeutic agent. 5. The overexpression of CPC genes, E2F1, and TMPO-AS1 in LUAD is strongly associated with reduced infiltration of CD4⁺ T cells, indicating their role in promoting an immunosuppressive tumor microenvironment. Graphical Abstract Schematic representation of the regulatory axis involving TMPO-AS1, hsa-let-7b-5p, and CPC genes in lung tissue. A Normal lung microenvironment: Under physiological conditions, low expression of lncRNA TMPO-AS1 and high levels of miRNA hsa-let-7b-5p maintain controlled expression of CPC genes. The upregulated miRNA binds CPC transcripts, leading to their degradation or translational repression, thereby preserving chromosomal stability and supporting an active immune microenvironment with effective CD4+ T cell infiltration. B Tumor lung microenvironment (LUAD associated with smoking): Chronic exposure to tobacco carcinogens leads to upregulation of TMPO-AS1 and downregulation of hsa-let-7b-5p. TMPO-AS1 sponges hsa-let-7b-5p, limiting its ability to suppress CPC transcripts, resulting in CPC overexpression. This promotes chromosomal instability, supports tumor growth, and contributes to the establishment of an immunosuppressive microenvironment characterized by reduced CD4+ T cell infiltratio
