ABSTRACT
Cancer cells reprogram their metabolisms to achieve high energetic requirements and produce precursors that facilitate uncontrolled cell proliferation. Metabolic reprograming involves not only the dysregulation in glucose-metabolizing regulatory enzymes, but also the enzymes engaging in the lipid and amino acid metabolisms. Nevertheless, the underlying regulatory mechanisms of reprograming are not fully understood. Non-coding RNAs (ncRNAs) as functional RNA molecules cannot translate into proteins, but they do play a regulatory role in gene expression. Moreover, ncRNAs have been demonstrated to be implicated in the metabolic modulations in breast cancer (BC) by regulating the metabolic-related enzymes. Here, we will focus on the regulatory involvement of ncRNAs (microRNA, circular RNA and long ncRNA) in BC metabolism, including glucose, lipid and glutamine metabolism. Investigation of this aspect may not only alter the approaches of BC diagnosis and prognosis, but may also open a new avenue in using ncRNA-based therapeutics for BC treatment by targeting different metabolic pathways.
Subject(s)
Breast Neoplasms , MicroRNAs , RNA, Long Noncoding , Breast Neoplasms/genetics , Female , Glucose/metabolism , Glutamine , Humans , Lipids , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics , RNA, Untranslated/metabolismABSTRACT
Methamphetamine (METH) is a highly addictive psychostimulant. Its abuse causes problems in cognition, attention, or psychiatric conditions such as psychosis. Prefrontal cortex is involved in many aspects of drug addiction and in mental disorders similar to those triggered by METH. Brain-derived neurotrophic factor (BDNF), plays important roles in modulating different aspects of addiction, and is implicated in psychiatric conditions reminiscent of those suffered by METH-abusers. Male Wistar rats were intra-peritoneally injected with METH (8 mg/kg/day) for 14 days while control group received normal saline. After extraction of prefrontal cortices, expression of BDNF IV splice variant and methylation level of its CpG island were evaluated. The relative expression of BDNF IV in METH-treated group was 2.15 fold higher than the control group. Seven out of 29 CpG sites were significantly hypomethylated in the METH group, although none survived Bonferroni adjustment. However, the overall methylation level of the 29 CpGs was significantly lower in METH cases than in controls. We discuss the importance of our results and its implications in detail.
