Background
Metabolic reprogramming is a hallmark of cancer. However, the roles of long noncoding RNAs (lncRNAs) in cancer metabolism, especially glucose metabolism remain largely unknown.
Results
In this study, we identified and functionally characterized a novel metabolism-related lncRNA, LINC00930, which was upregulated and associated with tumorigenesis, lymphatic invasion, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 was required for increased glycolysis activity and cell proliferation in multiple NPC models in vitro and in vivo. Mechanistically, LINC00930 served as a scaffold to recruit the RBBP5 and GCN5 complex to the PFKFB3 promoter and increased H3K4 trimethylation and H3K9 acetylation levels in the PFKFB3 promoter region, which epigenetically transactivating PFKFB3, and thus promoting glycolytic flux and cell cycle progression. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression.
Conclusions
Collectively, LINC00930 is mechanistically, functionally and clinically oncogenic in NPC. Targeting LINC00930 and its pathway may be meaningful for treating patients with NPC.
In the endometrium of women with recurrent implantation failure (RIF) and unexplained recurrent miscarriage (RM),the expression levels of homeobox A10 (HOXA10) and E-cadherin were positively correlated. To explore whether HOXA10 regulates E-cadherin during endometrial receptivity establishment, Ishikawa and RL95–2 cells were transfected with target-specific siRNA and overexpression plasmid of HOXA10. The expression levels of HOXA10 and E-cadherin were measured by western blot and qRT-PCR. Attachment assay of JEG-3 spheroids to endometrial cells were conducted to explore the adhesive functions after HOXA10 interfered. Chromatin immunoprecipitation assays and dual luciferase reporter were used to investigate the regulatory mechanism of HOXA10. CD1 mice were transfected with si-HOXA10 to confirm these results in vivo. In Ishikawa and RL95–2 cells, the expression of E-cadherin was positively correlated with HOXA10 when it was silenced/overexpressed. Consistently, the adhesion of endometrial epithelium cells and trophoblast cells was inhibited after HOXA10 was silenced, and exogenous restoration of E-cadherin expression reversed this effect to some extent. HOXA10 regulates the expression of E-cadherin by directly binding to a conserved motif (TGTACTAAAAA) located in the E-cadherin promoter region. In addition, after knockdown of HOXA10 in CD1 mice, both the implantation and live birth rates were decreased. In conclusion, HOXA10 can bind to the E-cadherin promoter region and directly regulate its expression, thereby improving endometrial receptivity and subsequently increasing the embryo adhesion and implantation.
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