ABSTRACT
Nonsmall-cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR-455-3p, and HDAC2 was explored by dual-luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR-455-3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)-mutant NSCLC cells. Moreover, inhibition of miR-455-3p exhibited the opposite effect. CRNDE bound with miR-455-3p, and HDAC2 was found to be targeted by miR-455-3p. Meanwhile, miR-455-3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR-455-3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR-455-3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylase 2/genetics , Histone Deacetylase 2/metabolism , Humans , Lung Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
PURPOSE: Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (nâ=â8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS). The impact of M1 and M2 type TAM (nâ=â5) on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR) â=â1.20 (95% confidence interval (CI), 1.14-1.28)] and bladder cancer [RRâ=â3.30 (95%CI, 1.56-6.96)] and with early clinical staging in patients with ovarian cancer [RRâ=â0.52 (95%CI, 0.35-0.77)]. Negative effects of TAM on OS was shown in patients with gastric cancer [RRâ=â1.64 (95%CI, 1.24-2.16)], breast cancer [RRâ=â8.62 (95%CI, 3.10-23.95)], bladder cancer [RRâ=â5.00 (95%CI, 1.98-12.63)], ovarian cancer [RRâ=â2.55 (95%CI, 1.60-4.06)], oral cancer [RRâ=â2.03 (95%CI, 1.47-2.80)] and thyroid cancer [RRâ=â2.72 (95%CI, 1.26-5.86)],and positive effects was displayed in patients with colorectal cancer [RRâ=â0.64 (95%CI, 0.43-0.96)]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.
