RESUMO
Long non-coding ribonucleic acids (LncRNAs) are recently known for their role in regulating gene expression and the development of cancer. Controversial results indicate a correlation between the tissue expression of LncRNA and LncRNA content of extracellular vesicles. The present study aimed to evaluate the expression of different LncRNAs in non-small cell lung cancer (NSCLC) patients in tumor tissue, adjacent non-cancerous tissue (ANCT), and exosome-mediated lncRNA. Tumor and ANCT, as well as serum samples of 168 patient with NSCLC, were collected. The GHSROS, HNF1A-AS1, HOTAIR, HMlincRNA717, and LINCRNA-p21 relative expressions in tumor tissue, ANCT, and serum exosomes were evaluated in NSCLC patients. Among 168 NSCLC samples, the expressions of GHSROS (REx = 3.64, p = 0.028), HNF1A-AS1 (REx = 2.97, p = 0.041), and HOTAIR (REx = 2.9, p = 0.0389) were upregulated, and the expressions of HMlincRNA717 (REx = −4.56, p = 0.0012) and LINCRNA-p21 (REx = −5.14, p = 0.00334) were downregulated in tumor tissue in contrast to ANCT. Moreover, similar statistical differences were seen in the exosome-derived RNA of tumor tissues in contrast to ANCT samples. A panel of the five lncRNAs demonstrated that the area under the curve (AUC) for exosome and tumor was 0.937 (standard error: 0.012, p value < 0.0001). LncRNAs GHSROS, HNF1A-AS1, and HOTAIR showed high expression in tumor tissue and exosome content in NSCLC, and a panel that consisted of all five lncRNAs improved diagnosis of NSCLC.
RESUMO
microRNAs (miRNAs or miRs) play key roles in different stages of chronic myeloid leukemia (CML) pathogenesis. The present study aimed to demonstrate whether miR-155 enables CD34+ CML cells to escape from the growth-inhibitory effects of TGF-ß1 and bone morphogenetic protein (BMP) signaling. Among differentially expressed miRNAs in CD34+ CML cells, miR-155 was highly up-regulated. QRT-PCR revealed an inverse correlation between miR-155 and two key members of the TGF-ß pathway-TGF-ßR2 and SMAD5. Results showed that SMAD5 is not only up-regulated through BMPs treatment, but recombinant TGF-ß1 can also induce SMAD5 in CML cells. We also demonstrated that TGF-ß1-mediated phosphorylation of SMAD1/5 was abolished by pre-treatment with the blocking TGF-ßR2 antibody, suggesting a possible involvement of TGF-ßR2. Additionally, overexpression of miR-155 significantly promoted the proliferation rate of CD34+ CML cells. Results showed that siRNA-mediated knockdown of SMAD5 had a promoting effect on CD34+ CML cell proliferation, suggesting that SMAD5 knock-down recapitulates the proliferative effects of miR-155. Importantly, TGF-ß1 and BMP2/4 treatment had inhibitory effects on cell proliferation; however, miR-155 overexpression enabled CD34+ CML cells to evade the anti-proliferative effects of TGF-ß1 and BMPs. Consistently, down-regulation of miR-155 augmented the promoting effects of TGF-ß1 and BMP signaling on inducing apoptosis in CD34+ CML stem cells. Our findings demonstrated that targeting of SMAD5 and TGF-ßR2 links miR-155 to TGF-ß signaling in CML. Overexpression of miR-155 enables CD34+ CML cells to evade growth-inhibitory effects of the TGF-ß1 and BMP signaling, providing new perspectives for miR-155 as a therapeutic target for CML.
