LncRNA-BLACAT1 Facilitates Proliferation, Migration and Aerobic Glycolysis of Pancreatic Cancer Cells by Repressing CDKN1C via EZH2-Induced H3K27me3

Abstract

Objective: To investigate the role of lncRNA-BLACAT1 in promoting H3K27 trimethylation of CDKN1C gene by recruiting EZH2 to regulate CCNE on glycolysis and mitochondrial oxidative phosphorylation of pancreatic cancer (PC) cells. Methods: Following bioinformatic prediction, EZH2 and BLACAT1 in PC cells were interfered, and cells proliferation, migration and invasion in each group were detected. Western blotting detected the expression of key proteins of mitochondrial complex. The sub-cellular localization of BLACAT1 was tested, followed by testing the binding of CDKN1C and BLACAT1 with EZH2, followed by in vivo verification. Results: Based on bioinformatic prediction, EZH2 and BLACAT1 were highly expressed in PC, while CDKN1C was lowly expressed (all P < 0.05). Interference with EZH2 and BLACAT1 inhibited cell proliferation, migration and aerobic glycolysis, and promoted mitochondrial oxidative phosphorylation (all P < 0.05). BLACAT1 promoted H3K27 trimethylation of CDKN1C through recruiting EZH2 (all P < 0.05). In vivo results showed that BLACAT1 interference inhibited tumor formation (all P < 0.05). Conclusion: Interference with BLACAT1 inhibits H3K27 trimethylation of CDKN1C gene by blocking EZH2 recruitment to promote CDKN1C expression and inhibit CCNE expression, thus suppressing PC cell proliferation, migration and aerobic glycolysis, and promoting mitochondrial oxidative phosphorylation.

A Glycolysis-Based Long Non-coding RNA Signature Accurately Predicts Prognosis in Renal Carcinoma Patients

“…MYC-mediated glycolysis of rectal tumor cells could be weakened with knocking out lncRNA LINRIS, which inhibited the progression of rectal cancer ( Wang Y. et al, 2019 ). The glycolysis process was verified to be the energy source of tumor cell growth and invasion, which was regulated by downstream transcriptional activities mediated by lncRNA ( Zhou et al, 2020 ). Glycolysis, as the main metabolic process in the cell metabolic microenvironment, participates in the proliferation of tumor cells.…”

The Role of Long Noncoding RNA AL161431.1 in the Development and Progression of Pancreatic Cancer

“…A search using the key words of lncRNA and pancreatic cancer in PubMed on July 28, 2020 yielded 589 publications, with the most relevant one dating back in 2011 (19). Most lncRNAs have been reported to promote the proliferation of pancreatic cancer through different signaling pathways (20)(21)(22)(23). In the case of lncRNA AL161431.1, its identified targets include miR-1252-5p, and the pathways include MAPK signaling in endometrial carcinoma and a competing endogenous RNA network in lung squamous cell carcinoma (7, 9; Table S2).…”

Role of long intergenic non-protein coding RNA 00152 in pancreatic cancer glycolysis via the manipulation of the microRNA-185-5p/Krüppel-like factor 7 axis

“…Glycolysis, a principal transcription factor metabolic course of ATP generation, has also been previously illustrated to promote cancer cell growth, while being activated in multiple human cancers, including PDAC [27]. Meanwhile, fluent glucose consumption and a substantial amount of lactic acid production are further known to be precipitated as a result of glycolysis functioning as a major process for fatal carcinoma to meet energy demands [19]. On the other hand, activation of HK2, PFKBF3 and PDK1 levels were previously indicated to augment glycolysis [28].…”

“…Human normal pancreatic ductal cells hTERT-HPNE (HPNE) and PC cell lines BxPC-3, Capan-1, PANC-1 and CFPAC-1 (all from American Type Culture Collection, Manassas, Virginia, USA) [19] were procured and cultured in Dulbecco's modified Eagle's medium (Gibco Company, Grand Island, NY, USA) containing fetal bovine serum (Gibco) at 37℃ saturated humidity (Thermo Fisher Scientific Inc., Waltham, MA, USA) in a humidified incubator with 5% CO2. Upon reaching 90% density, the cells were detached with 0.25% trypsin (T1300, Science & Technology Co., Ltd., Beijing, China) and subcultured at a ratio of 1: 3, with the passage 2 cells used for further experimentation.…”