Background: To undertake a bioinformatics analysis to identify abnormally expressed genes [also referred to as differentially expressed genes (DEGs)] and their functions in esophageal carcinoma (ESCA).Methods: DEGs (i.e., GSE100942, GSE17351, GSE26886, and GSE77861) were obtained from a gene expression omnibus database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using online tools from the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction network was then constructed based on the Search Tool for the Retrieval of Interacting Genes website. Cytoscape software was used to identify the top 20 DEGs located in the central region of the network. For the overall survival analysis, a Kaplan-Meier analysis was conducted of the Gene Expression Profiling Interactive Analysis website, and collagen (COL) 1A2 was selected to detect the molecular mechanism of COL1A2-small interfering ribonucleic acid (siRNA) in the following ESCA cell lines: Eca109 and TE-1. Next, the expression of COL1A2-messanger ribonucleic acid was determined using real-time quantitative polymerase chain reaction. The expression of COL1A2 was also verified by Western blot. Cell proliferation was measured by colony-forming and MTT assays, and migration and invasion by the transwell assay.Results: Based on the GEO database and screening out the hub gene, we identified that COL1A2 was abnormally expressed in ESCA. With a series of in vitro experiments, the expression of COL1A2 was defined as higher in Eca109 and TE-1.Conclusions: COL1A2 was highly expressed in ESCA tissue samples. Additionally, the proliferation and metastasis of Eca109 and TE-1 cell lines were significantly attenuated by siRNA-COL1A2-mediated small interference. Notably, the expression level of COL1A2 was obviously related to the Akt and epithelialmesenchymal transition (EMT) pathways.
Mammalian mitochondrial ribosomal proteins are a group of protein factors encoded by nuclear genes, responsible for the synthesis of proteins in mitochondria. As a member of mitochondrial ribosomal proteins, MRPL42 (mitochondrial ribosomal protein L42) belongs to 28S and 39S subunits. The current literature showed that its role in lung adenocarcinoma (LUAD) was not clear. We found that MRPL42 was highly expressed in early-stage LUAD tissues and cell lines, and remarkably related to the prognosis of patients. Knockdown of MRPL42 could reduce the proliferation and colonization, promote cell cycle arrest in G1/S phase, and weaken the migration and invasion ability of LUAD cells in vitro. Moreover, depletion of MRPL42 also inhibited tumor growth in vivo. Bioinformatics analysis found that YY1 may bind to the promoter region upstream of the MRPL42 gene to promote the transcription of MRPL42, which was verified by the ChIP and Dual luciferase reporter assay. QRT-PCR confirmed that knocking down YY1 could attenuate the expression of MRPL42. In summary, MRPL42 acts as an oncogene in LUAD, and its expression level is regulated by YY1.
Background: In recent years, there have been increasing reports that dysregulated circular RNAs (circRNAs) play a key role in the carcinogenesis of lung adenocarcinoma (LUAC). However, the role of circRNAs in early-stage LUAC is poorly understood. Methods:The Gene Expression Omnibus (GEO) database and qRT-PCR were used to verify the abnormal expression of circRNAs, miRNAs and genes in early-stage LUAC tissues. shRNA and miRNA inhibitor are designed and synthesized to knock down circ_104640 and microRNA (miR)-145-5p expression.CCK-8 assay, colony formation assay and flow cytometry were used to study the effect of circ_104640 on cell proliferation and apoptosis. Bioinformatics analysis, dual luciferase reporter assays and argonaute 2 (Ago2) RNA immunoprecipitation (RIP) assays were chosen to find out the potential target of circ_104640.Results: Based on the GEO database and tissue sample from our institution, we identified that the circRNA circ_104640, the miR-145-5p, and CCL20 (C-C motif chemokine ligand 20) were abnormally expressed in the tissues of early-stage LUAC. In vitro experiments showed that circ_104640 could exist stably in the cytoplasm, and a short pin RNA that targeted circ_104640 (sh-circ) inhibited cell growth and promoted apoptosis of LUAC cells. Dual luciferase reporter assays and Ago2 (RIP) assays confirmed the Ago2-dependent interaction of circ_104640 and miR-145-5p. In terms of mechanisms, we found that circ_104640 increased the expression of CCL20 by sponging miR-145-5p.Conclusions: Our research demonstrated that circ_104640 could accelerate the proliferation of LUAC cells, while inhibiting LUAC cell apoptosis. circ_104640 may be a potential novel biomarker and therapeutic target for early-stage LUAC.
With the popularity of neoadjuvant therapy as first-line treatment, especially for advanced squamous cell carcinoma (SCC), the focus has become accurate individualized treatment. Specifically, toxic side effects of traditional platinum-doublet chemotherapy are high, so treatment with pembrolizumab plus platinum-doublet chemotherapy is safer and more effective. Pembrolizumab is a humanized monoclonal IgG4 kappa anti-PD1 antibody. It is devoid of any cytotoxic activity among the drug effect. Pembrolizumab has been tested clinically in a series of KEYNOTE studies and 12 categories of malignancies have been tested to determine their clinical effects. A 64-year-old man with IIIA SCC of the lung without any surgical contraindications in the preoperative period successfully underwent radical resection and had a great prognosis after neoadjuvant treatment. Chest computed tomography (CT) showed that the left upper lung lesion, hilar and mediastinal lymph nodes were obviously smaller than before, meanwhile, obstructive pneumonia was significantly absorbed. No sign of metastasis was detected by head-abdominopelvic CT and bone scan. Although radiation pneumonitis was an adverse event after postoperative adjuvant therapy, symptoms were relieved with low-dose glucocorticoids. In conclusion, traditional chemotherapy with single agents alone has been gradually replaced by pembrolizumab plus platinum-doublet chemotherapy as a firstline therapy now.
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