Long Non-coding RNAs Involved in Metabolic Alterations in Breast and Prostate Cancers

Abstract

Breast and prostate cancers are the most prevalent cancers in females and males, respectively. These cancers exhibit sex hormone dependence and thus, hormonal therapies are used to treat these cancers. However, acquired resistance to hormone therapies is a major clinical problem. In addition, certain portions of these cancers initially exhibit hormone-independence due to the absence of sex hormone receptors. Therefore, precise and profound understanding of the cancer pathophysiology is required to develop novel clinical strategies against breast and prostate cancers. Metabolic reprogramming is currently recognized as one of the hallmarks of cancer, as exemplified by the alteration of glucose metabolism, oxidative phosphorylation, and lipid metabolism. Dysregulation of metabolic enzymes and their regulators such as kinases, transcription factors, and other signaling molecules contributes to metabolic alteration in cancer. Moreover, accumulating lines of evidence reveal that long non-coding RNAs (lncRNAs) regulate cancer development and progression by modulating metabolism. Understanding the mechanism and function of lncRNAs associated with cancer-specific metabolic alteration will therefore provide new knowledge for cancer diagnosis and treatment. This review provides an overview of recent studies regarding the role of lncRNAs in metabolism in breast and prostate cancers, with a focus on both sex hormone-dependent and -independent pathways.

Distal gene regulation mediated by non-coding RNAs contributes to germline risk for breast and prostate cancer

“…Common non-synonymous SNPs in HCG9 have previously been implicated in breast cancer GWAS (104). In addition, CEROX1 , a cataloged post-transcriptional regulator of mitochondrial catalytic activity, has been implicated in distal alterations of metabolic pathways in breast cancers (14, 105). ncRNAs prioritized in breast tumor GReX-associations with breast cancer risk mainly included micro- and snoRNAs.…”

“…However, as most ncRNA mechanisms in cancer tumorigenesis or progression have been categorized on a case-by-case basis (13, 14), mechanistic impacts of ncRNAs have not been explored systematically. Bioinformatics analyses that leverage high-throughput genomics have investigated the role of ncRNAs through computational target prediction or differential expression analyses.…”

“…ncRNAs have shown associations with the onset and progression of different cancers, are enriched in multiple tumor types, and are even therapeutic targets, as they act as regulators of genes in important tumorigenic or progressive networks 10 . Profiling and deep sequencing of ncRNAs have shown that perturbing ncRNA biogenesis affects amplification, deletion, and normal epigenetic and transcriptional regulation 10, 11, 13, 14 . Many ncRNAs act as oncogenes or antagonize tumor suppressors, but as most ncRNA mechanisms in cancer tumorigenesis or progression have been categorized on a case-by-case basis 13, 14 , mechanistic impacts of ncRNAs have not been explored systematically.…”

Long noncoding RNA RP11-241J12.3 targeting pyruvate carboxylase promotes hepatocellular carcinoma aggressiveness by disrupting pyruvate metabolism and the DNA mismatch repair system

“…In recent years, a handful of lncRNAs have been found to be closely connected with metabolism and DNA damage [28,29]. LncRNA NBR2 was induced by the LKB1-AMPK pathway under energy stress and lncRNA-JADE was induced after DNA damage [24,30].…”

Mechanisms of Apoptosis-Related Long Non-coding RNAs in Ovarian Cancer

“…Furthermore, lncRNAs are involved in gene regulation at post-transcriptional levels through interacting with mRNAs, miRNAs, and proteins ( Marchese et al, 2017 ). Intriguingly, lncRNAs play important roles in pathophysiology of various cancers ( Takayama and Inoue, 2016 ; Misawa et al, 2017 ; Arun et al, 2018 ; Mitobe et al, 2018 ; Kamada et al, 2020 ; Takeiwa et al, 2020 ). Particularly, several lncRNAs have been suggested to regulate the apoptosis of ovarian cancer cells ( Figure 1 and Table 1 ).…”