Abstract
Simple SummaryEpithelial ovarian cancer is an aggressive disease associated with relapse, resistance to chemotherapy, and high mortality rates. Recent discoveries have pointed out that long noncoding RNAs (lncRNAs) are potential biomarkers or therapeutic targets in several tumor types. However, fundamental knowledge about their functions and regulation is still lacking. Here, we present the current understanding of the interplay between lncRNAs and the epigenetic machinery influencing ovarian carcinogenesis. We also provide an overview of bioinformatics tools and databases that can be exploited for lncRNAs investigations. Altogether, this information can support the development of clinical initiatives to monitor disease progression or discover new strategies for the therapeutic management of ovarian cancer.Comprehensive large-scale sequencing and bioinformatics analyses have uncovered a myriad of cancer-associated long noncoding RNAs (lncRNAs). Aberrant expression of lncRNAs is associated with epigenetic reprogramming during tumor development and progression, mainly due to their ability to interact with DNA, RNA, or proteins to regulate gene expression. LncRNAs participate in the control of gene expression patterns during development and cell differentiation and can be cell and cancer type specific. In this review, we described the potential of lncRNAs for clinical applications in ovarian cancer (OC). OC is a complex and heterogeneous disease characterized by relapse, chemoresistance, and high mortality rates. Despite advances in diagnosis and treatment, no significant improvements in long-term survival were observed in OC patients. A set of lncRNAs was associated with survival and response to therapy in this malignancy. We manually curated databases and used bioinformatics tools to identify lncRNAs implicated in the epigenetic regulation, along with examples of direct interactions between the lncRNAs and proteins of the epigenetic machinery in OC. The resources and mechanisms presented herein can improve the understanding of OC biology and provide the basis for further investigations regarding the selection of novel biomarkers and therapeutic targets.
Highlights
Despite the advances in diagnosis and treatment in the last decades, ovarian cancer (OC) is still considered a clinical challenge due to the absence of improvements in long-term survival [1,2]
LncRNAs were previously recognized as noncoding genes, recent evidence has suggested that many of them contain small open reading frames that are strongly associated with ribosomes, which results in the translation of small peptides [36]
Acting by an unknown mechanism, the long noncoding RNAs (lncRNAs) UCA1 promotes the expression of kinase SRPK1 (SRSF protein kinase 1), which was associated with increased proliferation and reduced apoptosis of OC cells, favoring the development of cisplatin resistance [78]
Summary
Despite the advances in diagnosis and treatment in the last decades, ovarian cancer (OC) is still considered a clinical challenge due to the absence of improvements in long-term survival [1,2]. This suggests that most DNA sequences can be transcribed but not to encode proteins, generating noncoding RNAs (ncRNAs) This information has altered our perception of this RNA class and led to increased attention to their functional roles as regulators of physiological programs during development and human diseases, including cancer [17]. These ncRNAs are involved in regulatory and structural functions in cells and are usually are classified into two main categories according to the molecule size: long and short noncoding RNAs. Long noncoding RNAs (lncRNAs) are a group of transcripts with more than 200 nucleotides in length and were initially defined by the apparent absence of protein-coding potential [18]. We provided a guide for databases and tools that could help select disease-related lncRNAs for future functional studies and potential clinical applications
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