ABSTRACT
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have attracted much attention because of its regulatory role in occurrence and progression of tumors, including triple-negative breast cancer (TNBC). LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) has been explored in some cancers, whereas its function and molecular mechanism in TNBC remain unclear. METHODS: PITPNA-AS1 expression in TNBC tissues and cells was determined by RT-qPCR. TNBC cell viability, proliferation, migration, invasion were assessed with CCK-8, colony formation, wound healing, transwell assays. Cell apoptosis was evaluated by flow cytometry. Expression of EMT-related markers was detected by western blot analyses. The molecular mechanism of PITPNA-AS1 was explored by RNA pull down, luciferase reporter, RIP and ChIP assays. RESULTS: PITPNA-AS1 showed high expression levels in TNBC tissues and cells. PITPNA-AS1 knockdown suppressed TNBC cell viability, proliferation, migration, invasion in vitro and inhibited xenograft tumor growth in mice. Mechanistically, PITPNA-AS1 upregulated SIK2 expression by sponging miR-520d-5p and recruiting DDX54 protein. Results of rescue assays suggested that the inhibitive effects of silenced PITPNA-AS1 on TNBC cellular processes were partially rescued by overexpressing SIK2 or combination of miR-520d-5p inhibition and DDX54 overexpression. More importantly, we found that the upregulation of PITPNA-AS1 in TNBC cells was attributed to transcription factor MYBL2. CONCLUSION: PITPNA-AS1 activated by MYBL2 plays an oncogenic role in TNBC through upregulating SIK2.
Subject(s)
MicroRNAs , RNA, Long Noncoding , Triple Negative Breast Neoplasms , Animals , Cell Cycle Proteins , Cell Proliferation , DEAD-box RNA Helicases/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , Humans , Mice , MicroRNAs/genetics , Neoplasm Proteins , RNA, Long Noncoding/genetics , Trans-Activators , Triple Negative Breast Neoplasms/geneticsABSTRACT
In order to effectively control carbon dioxide emissions of motorized vehicles, it is very important to measure their carbon dioxide emission factors. The objective of this paper was to develop measurement models for the carbon dioxide emission factors of passenger cars. Road systems of downtown areas of four typical Chinese counties were explored and 12 types of basic road networks were recognized and defined. With PTV Vissim, microscopic traffic simulation models were set up for every type of basic road network, average speeds of the simulated cars were collected, and carbon dioxide emissions were calculated using MOVES (Motor Vehicle Emission Simulator) software. For model development, the paper put forth two compound explanatory variables: the weighted average of segment lengths and the sum of critical ratios of volume to saturation flow rate. Six functional relationships for the variables were tested and the double exponential function was proven to be the most appropriate. Finally, for each of the 12 types of basic road networks, a measurement model for carbon dioxide emission factors was calibrated using the double exponential function for the variables. The measurement models can be used to estimate the carbon dioxide emissions of passenger cars concerning potential improvement schemes impacting traffic demand and/or traffic supply.
