Abstract
Simple SummaryBreast and gynecological cancers, broadly termed as female-oriented cancers, are the primary cause of death among females in developed and developing countries. Tumor invasion and metastasis cause the aggressiveness of these cancer types. The occurrence and frequency of women’s cancers are associated with genetics, personal lifestyle, body shape, age, menopause status, history of exposure to carcinogens or viruses, and geographical habitat. Moreover, ncRNAs, especially lncRNAs, play an essential role in regulating cellular functions within such cancers. LncRNAs can play dual roles. They can either exert tumor-suppressive or oncogenic functions in women’s cancers. Accumulating evidence suggests that lncRNAs can be promising prognostic and diagnostic biomarkers and therapeutic targets in cancers. Thus, understanding the mechanism and role of lncRNAs might provide new opportunities for diagnosing and treating female-oriented cancers. In this review, we discuss the worldwide incidence of breast and gynecological cancers, including endometrial, cervical, ovarian, vaginal, vulvar cancers, and GTN among women. We further provide various perspectives on the association of some lncRNAs, i.e., HOTAIR, NEAT1, H19, MALAT1, and MEG3, in terms of invasion, proliferation, metastasis, apoptosis, and drug resistance of breast and gynecological cancers based on recent discoveries. Finally, we present insight and prospects into the potential of these lncRNAs for evaluating the prognosis, diagnosis, and treatment of such cancers.Recent advances in molecular biology have discovered the mysterious role of long non-coding RNAs (lncRNAs) as potential biomarkers for cancer diagnosis and targets for advanced cancer therapy. Studies have shown that lncRNAs take part in the incidence and development of cancers in humans. However, previously they were considered as mere RNA noise or transcription byproducts lacking any biological function. In this article, we present a summary of the progress on ascertaining the biological functions of five lncRNAs (HOTAIR, NEAT1, H19, MALAT1, and MEG3) in female-oriented cancers, including breast and gynecological cancers, with the perspective of carcinogenesis, cancer proliferation, and metastasis. We provide the current state of knowledge from the past five years of the literature to discuss the clinical importance of such lncRNAs as therapeutic targets or early diagnostic biomarkers. We reviewed the consequences, either oncogenic or tumor-suppressing features, of their aberrant expression in female-oriented cancers. We tried to explain the established mechanism by which they regulate cancer proliferation and metastasis by competing with miRNAs and other mechanisms involved via regulating genes and signaling pathways. In addition, we revealed the association between stated lncRNAs and chemo-resistance or radio-resistance and their potential clinical applications and future perspectives.
Highlights
The long non-coding RNAs are one of two basic classes of the non-coding RNAs, arbitrarily defined as ncRNA transcripts with at least 200 base pairs that do not encode proteins [1]
Cytoplasmic long non-coding RNAs (lncRNAs) are generally involved in regulating mRNA turnover, alternative splicing, post-transcriptional regulation, protein stability, microRNA sponging, and the regulation of signaling pathways [10]
(ii) Antisense intergenic lncRNAs are located between two coding genes while transcribed from the antisense strand of a protein-coding gene, e.g., HOTAIR lncRNA
Summary
The long non-coding RNAs (lncRNAs) are one of two basic classes of the non-coding RNAs (ncRNA), arbitrarily defined as ncRNA transcripts with at least 200 base pairs (bp) that do not encode proteins [1]. The current Gencode annotation approximates nearly 17,952 lncRNA genes and 48,438 transcripts in humans, widely associated with cellular processes during normal development and physiology [4,5]. Despite the normal physiological regulation, disruption of lncRNA’s expression has been intrinsically linked with the occurrence and development of a range of diseases, including cancer It led to the raised interest in studying lncRNAs with the prospect of discovering novel therapeutic and diagnostic strategies [16]. (ii) Antisense intergenic lncRNAs are located between two coding genes while transcribed from the antisense strand of a protein-coding gene, e.g., HOTAIR lncRNA It belongs to a subclass of lincRNA that can decrease radiosensitivity in laryngeal cancer patients by regulating miR-454-3p [53]. Such circRNAs are more stable than linear ncRNAs since their circular structure is resistant to degradation by RNA decay machinery [64]
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