Meta-analysis of microarray data to determine gene indicators involved in cisplatin resistance in non-small cell lung cancer.

BACKGROUND: Lung cancer is a major cause of cancer-related mortality worldwide, with a 5-year survival rate of approximately 22%. Cisplatin is one of the standard first-line chemotherapeutic agents for non-small cell lung cancer (NSCLC), but its efficacy is often limited by the development of resistance. Despite extensive research on the molecular mechanisms of chemoresistance, the underlying causes remain elusive and complex. AIMS: We analyzed three microarray datasets to find the gene signature and key pathways related to cisplatin resistance in NSCLC. METHODS AND RESULTS: We compared the gene expression of sensitive and resistant NSCLC cell lines treated with cisplatin. We found 274 DEGs, including 111 upregulated and 163 downregulated genes, in the resistant group. Gene set enrichment analysis showed the potential roles of several DEGs, such as TUBB2B, MAPK7, TUBAL3, MAP2K5, SMUG1, NTHL1, PARP3, NTRK1, G6PD, PDK1, HEY1, YTHDF2, CD274, and MAGEA1, in cisplatin resistance. Functional analysis revealed the involvement of pathways, such as gap junction, base excision repair, central carbon metabolism, and Notch signaling in the resistant cell lines. CONCLUSION: We identified several molecular factors that contribute to cisplatin resistance in NSCLC cell lines, involving genes and pathways that regulate gap junction communication, DNA damage repair, ROS balance, EMT induction, and stemness maintenance. These genes and pathways could be targets for future studies to overcome cisplatin resistance in NSCLC.

Acute Kidney Injury (AKI) in COVID-19: In silico Identification of LncRNA-MiRNA-Gene Networks and Key Transcription Factors.

PURPOSE: Acute kidney injury (AKI) accounts for up to 29% of severe COVID-19 cases and increases mortality among these patients. Viral infections participate in the pathogenesis of diseases by changing the expression profile of normal transcriptome. This study attempts to identify LncRNA-miRNA-gene and TF-gene networks as gene expression regulating networks in the kidney tissues of COVID-19 patients. METHODS: In this analysis, four kidney libraries from the GEO repository were considered. To conduct the preprocessing, Deseq2 software in R was used for the purpose of data normalization and log2 transformation. In addition, pre- and post-normalization, PCA and box plots were developed using ggplot2 software in R for quality control. The expression profiles of the kidney samples of COVID-19 patients and control individuals were compared using DEseq2 software in R. The considered significance thresholds for DEGs were Adj P value < 0.05 and |logFC| >2. Then, to predict molecular interactions in lncRNA-miRNA-gene networks, different databases, including DeepBase v3.0, miRNATissueAtlas2, DIANA-LncBase v3, and miRWalk, were used. Furthermore, by employing ChEA databases, interactions at the TF-Gene level were obtained. Finally, the obtained networks were plotted using Stringdb and Cytoscape v8. RESULTS: Results obtained from the comparison of the post-mortem kidney tissue samples of the COVID-19 patients with the healthy kidney tissue samples showed significant changes in the expression of more than 2000 genes. In addition, predictions regarding the miRNA-gene interaction network based on DEGs obtained from this meta-analysis showed that 11 miRNAs targeted the obtained DEGs. Interestingly, in the kidney tissue, these 11 miRNAs interacted with LINC01874, LINC01788, and LINC01320, which have high specificity for this tissue. Moreover, four transcription factors of EGR1, SMAD4, STAT3, and CHD1 were identified as key transcription factors regulating DEGs. Taken together, the current study showed several dysregulated genes in the kidney of patients affected with COVID-19. CONCLUSION: This study suggests lncRNA-miRNA-gene networks and key TFs as new diagnostic and therapeutic targets for experimental and preclinical studies.

The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.

In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy.