RESUMEN
The transcription factor E2F1 induces both proliferation and apoptosis and is a critical downstream target of the tumor suppressor RB. Long non-coding RNAs (lncRNAs) are major regulators of many cellular processes, including cell cycle progression and cell proliferation. However, the mode of action as well as the transcriptional regulation of most lncRNAs are only beginning to be understood. Here, we report that a novel human lncRNA, LAPAS1, is an E2F1- regulated lncRNA that affects S phase progression. Inhibition of LAPAS1 expression increases percentage of S phase cells, and its silencing in synchronized cells delays their progression through S phase. In agreement with its suggested role in cell cycle progression, prolonged inhibition of LAPAS1 attenuates proliferation of human cancer cells. Our data demonstrate that LAPAS1 predominantly functions in trans to repress expression of Sphingolipid Transporter 2 (SPNS2). Importantly, knockdown of SPNS2 rescues the effect of LAPAS1 silencing on cell cycle and cell proliferation. Notably, low levels of LAPAS1 are associated with increased survival of kidney cancer patients. Summarily, we identify LAPAS1 as a novel E2F-regulated lncRNA that has a potential role in human cancer and regulates cell-cycle progression and cell proliferation, at least in part, via regulation of SPNS2.
RESUMEN
OBJECTIVE: Activated clotting time (ACT)-based heparin dosing during percutaneous intervention (PCI) is recommended by Society guidelines. However, the relationship between ACT and outcome in the setting of elective PCI has not been sufficiently studied. We sought to evaluate the in-hospital outcome of patients undergoing elective PCI while receiving fixed-dose heparin without ACT measurement versus those with ACT-guided management. METHODS: This retrospective study included consecutive patients undergoing elective PCI in a single-center between 11/2015 and 12/2018. Patients were divided into two groups, depending on whether ACT was measured. Heparin-only anticoagulation and non-femoral procedures were allowed. Patient demographics, procedural data and in-hospital outcomes were collected. The primary outcome was in-hospital major adverse cardiovascular events (MACE), secondary (safety) outcomes were in-hospital definite stent thrombosis, Bleeding Academic Research Consortium bleeding, access-related complications (any) as well as peri-procedural complications. RESULTS: In total, 500 procedures were included in the study, 151 ACT and 349 fixed-dose. Patient demographics and medical history in both groups were well balanced, but those having ACTs were younger (63.2 ± 10.9 vs. 66.5 ± 11.3; P = 0.003) and less likely to have a history of coronary artery disease (74 vs. 82%; P = 0.032) or kidney failure. Procedural data were similar; however, total heparin dose and procedure length were higher in the ACT group (6232 ± 1388 vs.5032 ± 417 units; P < 0.001; 40.1 ± 14.0 vs. 30.3 ± 12.7 min; P < 0.001). Primary and secondary outcome events were rare and similar (MACE 1.1 vs. 1.3%; P = 0.86). CONCLUSIONS: A fixed-dose heparin injection (5000 IU) approach for elective PCI while omitting ACT offers slightly shortened procedural time and similar in-hospital safety profile.