Systematic identification of clinically relevant miRNAs for potential miRNA-based therapy in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD), the most common histological type of non-small cell lung cancer, is one of the most malignant and deadly diseases. Current treatments for advanced LUAD patients are far from ideal and require further improvements. Here, we utilized a systematic integrative analysis of LUAD microRNA sequencing (miRNA-seq) and RNA-seq data from The Cancer Genome Atlas (TCGA) to identify clinically relevant tumor suppressor miRNAs. Three miRNA candidates (miR-195-5p, miR-101-3p, and miR-338-5p) were identified based on their differential expressions, survival significance levels, correlations with targets, and an additive effect on survival among them. We further evaluated mimics of the three miRNAs to determine their therapeutic potential in inhibiting cancer progression. The results showed not only that each of the miRNA mimics alone but also the three miRNA mimics in combination were efficient at inhibiting tumor growth and progression with equal final concentrations, meaning that the three miRNA mimics in combination were more effective than the single miRNA mimics. Moreover, the combined miRNA mimics provided significant therapeutic effects in terms of reduced tumor volume and metastasis nodules in lung tumor animal models. Hence, our findings show the potential of using the three miRNAs in combination to treat LUAD patients with poor survival outcomes.

Systematic Analysis and Validation of the Prognosis, Immunological Role and Biology Function of the Ferroptosis-Related lncRNA GSEC/miRNA-101-3p/CISD1 Axis in Lung Adenocarcinoma

“…Similarly, miRNA-101-3p was reported to inhibit both proliferative and migratory capabilities of gastric carcinoma cells and enhance apoptosis via PIM-1 expression modulation ( Wu et al, 2019 ). Indeed, in an LUAD setting of miRNA-101-3p downregulation, overexpression of miR-101-3p mimics was reported to reduce rates of tumor growth and progression in vitro ( Liu et al, 2021 ). In this study, data obtained from various public databases were used to illustrate novel mRNA–miRNA–lncRNA interactions (namely, the lncRNA GSEC/miR-101-3p/ATP5MC3/PGD/CISD1 axis) detailing modulation of FRG expression following the ceRNA hypothesis (Figure 11 ).…”

Noncoding RNA-Mediated High Expression of PFKFB3 Correlates with Poor Prognosis and Tumor Immune Infiltration of Lung Adenocarcinoma

“…They are involved in post-transcriptional gene expression regulation in animals and plants. 31 To explore the possible upstream molecule of PFKFB3, we introduced three programs—miRDB, Targetscan, and miRWalk databases. At the end, seven miRNAs were obtained.…”

RP11‐367G18.1 V2 enhances clear cell renal cell carcinoma progression via induction of epithelial–mesenchymal transition

“…After inoculation at 30–35 days, the mice were sacrificed, and the tumor volume was measured. Tumor volume was calculated using a formula: π/6 × length × width × height 22 …”

“…Tumor volume was calculated using a formula: π/6 × length × width × height. 22 2.10 | Tail vein and orthotopic metastatic mouse models Male NOD-SCID mice (6-week-old, National Science Council Animal Center) were used to assess metastatic ability. For tail vein metastatic mouse models, Caki-1 cells were intravenously injected (1 × 10 6 cells) into the tail veins of NOD-SCID mice.…”