Search

Introduction: ABL2 contributes to the oncogenic potential of cancers, pointing to its inhibition as a possible strategy against malignant diseases. Bioinformatics prediction of upstream effector miR-30a-5p for ABL2 allowed us to hypothesize and then validate mechanistic actions of miR-30a-5p in lung adenocarcinoma (LUAD). Materials and methods: The ABL2 expression in LUAD was analyzed in the TCGA data, clinical samples, and cell lines. The shRNA-mediated silencing of ABL2 was introduced to illustrate its effect on malignant phenotypes of LUAD cells. The binding affinity between ABL2 and miR-30a-5p was verified by luciferase activity and RNA pull-down assay. Ectopic expression, knockdown methods, and PI3K inhibitor LY294002 were used to investigate their effects on in vitro biological characteristics and in vivo tumor growth of LUAD cells. Using nude mouse lung adenocarcinoma in situ and brain metastasis models to validate the inhibitory effect of miR-30a-5p on LUAD by regulating the ABL2/PI3K/AKT signaling axis. Results: High expression of ABL2 and poor expression of miR-30a-5p were noticed in LUAD tissues and cell lines. Importantly, miR-30a-5p was demonstrated to target and downregulate ABL2, subsequently inactivating the PI3K/AKT pathway. miR-30a-5p inhibited the malignant phenotypes of LUAD cells by inhibiting ABL2 expression and inactivating the PI3K/AKT pathway. For in vivo experiments, miR-30a-5p was substantiated to thwart tumor tumorigenesis by regulating the ABL2/PI3K/AKT axis. In addition, miR-30a-5p suppresses the occurrence and development of in situ lung cancer and brain metastasis via the ABL2/PI3K/AKT signaling pathway. Conclusion: This study underscores the inhibitory role of miR-30a-5p in LUAD through the ABL2/PI3K/AKT axis, which may be a viable target for LUAD treatment. [ABSTRACT FROM AUTHOR]

LINC00488 confers oncogenic activity in the progression of some tumors. Hence, the target of the study was about to specify LINC00488-mediated network in retinoblastoma (RB). LINC00488 expression was tested in RB clinical tissues. siRNA targeting LINC00488 or miR-30a-5p mimic was introduced into RB cell line (Y79) to observe cellular biological functions. The relationship between LINC00488, miR-30a-5p and EPHB2 was verified. Afterward, the role of miR-30a-5p involved in RB through targeted regulation of EPHB2 was probed in vitro and in vivo. LINC00488 was induced in RB tissue and cells. LINC00488 knockdown or miR-30a-5p upregulation depressed the malignant activities of Y79 cells. LINC00488 could sponge miR-30a-5p that targeted EPHB2. EPHB2, and EPHB2 overexpression counteracted miR-30a-5p restoration-induced inhibition of Y79 cell development in vitro and in vivo. LINC00488 induces tumorigenicity in RB by binding to miR-30a-5p to target EPHB2, which may offer a new clue of RB treatment from an lncRNA–miRNA–mRNA network. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a fatal and currently incurable cardiopulmonary disease. Numerous microRNAs (miRNAs) serve important roles in the development of PAH. While the expression of miR-30a-5p was downregulated in the lung tissue of rats in a pulmonary hypertension rat model, the expression pattern and function of miR-30a-5p in human PAH remain unclear. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to examine miR-30a-5p and chitinase-3-like protein 1 (YKL-40) mRNA expression levels. The expression levels of YKL-40 and apoptosis-associated proteins were measured by western blot analysis. Cell proliferation assays and flow cytometry analysis were performed to examine cell proliferation and apoptosis, respectively. The association between miR-30a-5p and YKL-40 was determined by a luciferase reporter assay, RT-qPCR and western blot analysis. The relative expression levels of miR-30a-5p in plasma were increased in patients with PAH [median=13.23 (25th percentile=6.388, 75th percentile=21.91)] compared with normal controls [median=2.25 (25th percentile=1.4, 75th percentile=3.7). The expression of miR-30a-5p was significantly downregulated while the protein expression of YKL-40 was significantly upregulated in hypoxia-induced human pulmonary artery endothelial cells (HPAECs) when compared with the hypoxia-induced group at 0 h. miR-30a-5p overexpression promoted HPAEC growth and inhibited apoptosis of HPAECs under hypoxia. A miR-30a-5p mimic decreased the luciferase activity of a luciferase reporter construct containing YKL-40 3′-untranslated region and also decreased YKL-40 protein expression. YKL-40 overexpression partly alleviated the effects of miR-30a-5p upregulation on proliferation and apoptosis of HPAECs under hypoxia. In conclusion, the data indicated that miR-30a-5p promoted cell growth and inhibited apoptosis of HPAECs under hypoxia by targeting YKL-40. Therefore, the miR-30a-5p/YKL-40 axis may provide a potential target for the development of novel PAH therapies. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are a class of small non-coding RNAs of 18-25 nucleotides in length that serve as key regulators in the development and progression of human cancers. Recently, miR-30b-5p, as a member of the miR-30 family, has been reported to act as a tumor suppressor in gastric cancer. However, the expression and function of miR-30a-5p in gastric cancer, as well as the corresponding underlying mechanism, remain unknown. In the present study, it was demonstrated that the expression of miR-30a-5p was significantly reduced in gastric cancer tissues (n=43) compared with normal gastric tissues (n=10; P<0.01). Similarly, miR-30a-5p was significantly downregulated in the gastric cancer cell lines AGS, HGC27, BGC823 and SGC7901, when compared with the normal gastric mucosa epithelial cell line GES-1 (P<0.01). In addition, overexpression of miR-30a-5p significantly inhibited the proliferation and invasion of AGS cells (P<0.01). Insulin-like growth factor 1 receptor (IGF-1R) was identified as a novel target of miR-30a-5p, and the protein expression of IGF-1R was negatively regulated by miR-30a-5p in AGS cells (P<0.01). Furthermore, overexpression of IGF-1R significantly reversed the inhibitory effect of miR-30a-5p on the proliferation and invasion of AGS cells (P<0.01), indicating that IGF-1R was involved in miR-30a-5p-mediated proliferation and invasion of AGS cells. It was also observed that the expression of IGF-1R mRNA was upregulated in gastric cancer tissues compared with normal gastric tissues (P<0.01), and its levels of expression were reversely correlated with that of miR-30a-5p in gastric cancer tissues (R²=0.3892; P<0.01). Collectively, these data suggest that miR-30a-5p inhibits the growth and metastasis of gastric cancer by directly targeting IGF-1R. Therefore, the miR-30a-5p/IGF-1R axis may be a potential therapeutic target in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]