Inflammation and excessive proliferation of vascular smooth muscle cells (VSMCs) have key roles in various vascular disorders, including restenosis, atherosclerosis and pulmonary artery hypertension. However, the underlying mechanism remains unclear. The present study investigated the role of nuclear factor-κB (NF-κB) and microRNA (miRNA) in the regulation of VSMC proliferation under inflammatory conditions. It was demonstrated that miR-17 stimulated the proliferation of VSMCs, enhanced cell cycle G1/S transition, and increased levels of proliferating cell nuclear antigen and E2F1. By directly targeting the retinoblastoma (RB) protein mRNA-3′ untranslated region, miR-17 suppressed the expression of RB. Activation of NF-κB p65 resulted in increased miR-17 expression in VSMCs, whereas inactivation of NF-κB p65 resulted in decreased expression of miR-17 in VSMCs. NF-κB p65 signalling directly regulates miR-17 promoter activity. NF-κB p65 activation also suppressed RB expression, which was abrogated by miR-17 inhibitor. Taken together, the present results indicated that VSMC proliferation is regulated by activation of the NF-κB p65/miR-17/RB pathway. As NF-κB p65 signalling is activated in and is a master regulator of the inflammatory response, the present findings may provide a mechanism for the excessive proliferation of VSMCs under inflammation during vascular disorders and may identify novel targets for the treatment of vascular diseases.
The expression levels of microRNA‑31 (miR‑31) and LOC554202 have been previously investigated in colorectal cancer (CRC) and their oncogenic and/or tumor suppressive roles have been described. The aim of the present study was to examine the role of miR‑31 and its host gene LOC554202 in the prognosis of patients with CRC. Patients with CRC treated with oxaliplatin‑based chemotherapy between June 2005 and March 2010 were recruited to the First Affiliated Hospital of China Medical University. Tumor and adjacent mucosal tissues were collected. The detection of miR‑31 and/or LOC554202 was performed with probe hybridization targeting. Correlation analysis was performed among the expression levels of miR‑31, LOC554202, and their association with clinicopathological parameters and/or survival rates. miR‑31 and LOC554202 were expressed at high levels in CRC (P<0.01) compared with adjacent intestinal mucosa. A linear correlation was noted for the two markers in CRC tissues (P<0.01). The expression of miR‑31 was significantly higher in adenocarcinoma than in the adjacent intestinal mucosa (P<0.01), whereas the expression of LOC554202 was significantly higher in the adenocarcinoma and the rectal cancer tissue regions (P<0.01). The high expression levels of miR‑31 and LOC554202 were associated with high disease‑free survival (DFS) and overall survival (OS) rates (P<0.05). Associations between the increase in DFS and OS and the elevated expression levels of miR‑31 and LOC554202 were present in patients with colon cancer but not in patients with rectal cancer (P<0.05). These data indicated that miR‑31 and LOC554202 may be potential markers for evaluation of the prognosis of patients treated with oxaliplatin‑based chemotherapy.
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