MicroRNAs as Biomarkers for Early Diagnosis, Prognosis, and Therapeutic Targeting of Ovarian Cancer

Abstract

Ovarian cancer is the major cause of gynecologic cancer-related mortality. Regardless of outstanding advances, which have been made for improving the prognosis, diagnosis, and treatment of ovarian cancer, the majority of the patients will die of the disease. Late-stage diagnosis and the occurrence of recurrent cancer after treatment are the most important causes of the high mortality rate observed in ovarian cancer patients. Unraveling the molecular mechanisms involved in the pathogenesis of ovarian cancer may help find new biomarkers and therapeutic targets for ovarian cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression, mostly at the posttranscriptional stage, through binding to mRNA targets and inducing translational repression or degradation of target via the RNA-induced silencing complex. Over the last two decades, the role of miRNAs in the pathogenesis of various human cancers, including ovarian cancer, has been documented in multiple studies. Consequently, these small RNAs could be considered as reliable markers for prognosis and early diagnosis. Furthermore, given the function of miRNAs in various cellular pathways, including cell survival and differentiation, targeting miRNAs could be an interesting approach for the treatment of human cancers. Here, we review our current understanding of the most updated role of the important dysregulation of miRNAs and their roles in the progression and metastasis of ovarian cancer. Furthermore, we meticulously discuss the significance of miRNAs as prognostic and diagnostic markers. Lastly, we mention the opportunities and the efforts made for targeting ovarian cancer through inhibition and/or stimulation of the miRNAs.

Strategy for Pre-Clinical Development of Active Targeting MicroRNA Oligonucleotide Therapeutics for Unmet Medical Needs

“…Several membrane receptors often overexpressed in OC cells have emerged as potential targets for receptor-mediated therapies [ 79 ]. Given the roles of miRNAs in various cellular pathways, including cell survival and differentiation, targeting miRNAs could be a viable approach for the treatment of human cancers, such as OC, through the inhibition and/or stimulation of miRNAs [ 80 ]. Our end goal is to develop safe, effective and convenient miRNA-based therapies to cure OC.…”

Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors

“…The lncRNA XIST is found to be downregulated in OC to confer paclitaxel resistance, and mechanistic study shows that it increases Lysine N-methyltransferase 2C (KMT2C) via targeting miR-93-5p to regulate CD44+/CD24-OSCs [135] . lncRNA-H19 sponges miR-29b-3p to promote STAT3 to promote carboplatin-resistant EOC [136] . Several miRNAs are also known to regulate the OCSCs.…”

Tumor Promoting Role of NRIP1 in Oral Squamous Cell Carcinoma: The Involvement of NSD2-Mediated Histone Methylation of DGCR8

“…Moreover, we further obtained via bioinformatics tools that DGCR8 microprocessor complex subunit (DGCR8) shows close correlation with NSD2. DGCR8 is an RNA-binding protein that plays key roles in the biogenesis of canonical microRNAs by coordinating with the ribonuclease III enzyme Drosha, which is also closely linked to the pathogenesis of cancers (Lu et al 2020, Mirahmadi et al 2021). However, the exact role of DGCR8 in OSCC remains untouched.…”