We also intended to determine the possible

We also intended to determine the possible mechanism underlying EZH2 upregulation in the PC. Although no recurrent mutations of EZH2 have been described in CLL [27, 28, 29], we aimed to rule out the possibility of activating mutations in the background of EZH2 overexpression. We detected no mutations in the known hot spots of EZH2 (exons 16 and 18). EZH2 expression is also known to be induced by c-Myc through repression of its negative regulator miR-26a or by activation of transcription factor E2F1 [30, 31]. Elevated expression of c-Myc protein in PCs of CLL/SLL has been described previously [25]. E2F1 is also regulated by the tumorsuppressor Rb; inactivation of the Rb by phosphorylation leads to release and subsequent increased activity of E2F1 [32, 33]. Based on the data above, we analyzed these regulatory pathways by immunohistochemistry of c-Myc, pRB and E2F1, and by quantitative RT-PCR of miR-26a in cases of CLL/SLL and compared the expression levels between the PCs and IF areas. All examined proteins showed significantly higher expression with mainly the larger akt pathway showing positivity, while miR-26a was downregulated in the PCs compared to IFs. These results indicate that c-Myc/E2F1, c-Myc/miR-26a and pRb/E2F1 pathways may all be responsible for EZH2 overexpression in the PCs of lymph nodes of CLL/SLL. Our observation, that protein positivity was predominantly confined to the prolymphocytes and paraimmunoblasts strongly suggests that the levels of EZH2 and its regulators are overexpressed in the same cells. Rabello et al. found elevated EZH2 expression in CLL patients with cytogenetic abnormalities compared to those with normal karyotype [20]. In our cohort no such association could be detected with EZH2, however, low expression of its negative regulator miR-26a in the PCs correlated with the presence of chromosomal aberrations and loss of 17p.
Acknowledgement
Introduction Prostate cancer functions as one of the most common malignant tumors accompanied by extensive morbidity worldwide (Brito et al., 2017; Fei, 2017). Although numerous progress have proved for the diagnostic or therapeutic means in recent years, the long term prognosis or five-year survival rate of prostate cancer patients is still inconvenient or undesirable (Poorthuis et al., 2017; Chen and Sheng, 2018). As is well-known that the metastasis and invasion could cause the recurrence and intractable therapy, therefore, the potential molecular mechanism of prostate cancer is necessary to clear out to improve the prognosis (Sebesta and Anderson, 2017). Long noncoding RNAs (lncRNAs) are a group of RNAs being characterized with longer than 200 nucleotides and its vital functions on the epigenetic regulation (J.X. Wang et al., 2018; Y. Wang et al., 2018; Zhang et al., 2018). In the pathophysiogenesis of prostate cancer, increasing number of lncRNAs has been identified by researchers, referring to transcriptional regulation and post-transcriptional regulation. For example, overexpression of lncRNA MIR222HG is associated with prostate cancer progression and increases the androgen-independent cell growth (Sun et al., 2018). For another example, SNHG7 expression was significantly up-regulated in prostate cancer tissue and cell lines, exerting its oncogenic roles via miR-503/Cyclin D1 to regulate cell cycle arrest at G0/G1 phase and tumor growth (Qi et al., 2018). The increasing roles of lncRNAs in the prostate cancer tumorigenesis are gradually reported (Zhao et al., 2018). However, there are still numerous doubtful points for the molecular mechanism. In this study, we focus on the function of lncRNA FOXC2-AS1 in the prostate cancer origination, and investigate its molecular mechanism. FOXC2-AS1 is found to be up-regulated in the prostate cancer tissue and cells, promoting the pathogenesis via targeting miR-1253/EZH2.
Materials and methods
Results
Discussion Long noncoding RNAs (lncRNAs) act as a shining star in the research of epigenetics, which has be verified by increasing evidence (Iordache et al., 2018). For the prostate cancer oncogenesis, researchers have reported increasing number of lncRNAs, oncogenic or anti-cancer roles, in the pathogenesis with multiple functions (F et al., 2017). The proliferation, metastasis and invasion make the therapy for prostate cancer be inflexible, and result in the recrudesce and multiple-drug resistance (Xu et al., 2018). Obviously, there are complex molecular interaction mechanisms in the prostate cancer tumorigenesis. Therefore, prostate cancer ranks as one of the most common malignant tumors accompanied by extensive morbidity worldwide.