Abstract
Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs’ regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.
Highlights
Ovarian cancer (OC) is the second most common cause of death worldwide due to gynecological cancers
The most frequently identified regulatory mechanism of action of long non-coding RNAs (lncRNAs) is acting as competing endogenous RNAs with micro RNAs (miRNAs), which regulate the fate of mRNAs that encode proteins involved in cancer
These regulatory relationships among ncRNAs are not mutually exclusive, and several lncRNAs can act on the same miRNA targets, such as ANRIL, H19, and HOST2 that sequester let-7a, which regulates the expression of HMGA2, c-Myc, IGF2BP, Dicer and IMP3; and HOTAIR, lncARSR, and MALAT1 that sequester miR-200c, which modulates the expression of epithelial-to-mesenchymal transition (EMT) regulators such as ZEB1/2 or Snail
Summary
Ovarian cancer (OC) is the second most common cause of death worldwide due to gynecological cancers. Within EOC, five histological subtypes can be distinguished: high-grade serous, low-grade serous, mucinous, clear-cell and endometrioid They are distinguished on the basis of histological structure; mutations in certain proto-oncogenes or tumor suppressor genes; chemosensitivity; spreading behavior; and the most worrisome, prognosis. The peculiarity of lncRNAs is their ability to regulate gene expression at many different levels, by modulating chromatin remodeling, transcription, and alternative splicing, and generating micro RNAs (miRNAs) or producing short biologically active peptides [5]. They actively participate in all the events involved in tumor development and spread, and even in treatment resistance in bladder cancer, colorectal cancer, multiple myeloma and others, including OC [6]. Future work required in the field is discussed along with some concluding remarks
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