Dysregulation of lncRNA–miRNA–mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer

Abstract

Ovarian cancer (OC) is one of the most common types of cancer among malignancies of the female reproductive system. This pathology is asymptomatic until advanced stages and has a poor prognosis. Our study aimed to search for lncRNA–miRNA–mRNA competing triplets that promote ovarian tumorigenesis. For this purpose, we analyzed tumor samples from the TCGA database and verified the results experimentally in a set of 46 paired samples of tumor and matched histologically unchanged ovarian tissues from OC patients. The list of RNAs selected in silico for experimental studies included 13 mRNAs, 10 lncRNAs, and 5 miRNAs related to epithelial–mesenchymal transition and angiogenesis. We evaluated the expression of these RNAs by qRT-PCR and assessed the correlation between levels of miRNAs, mRNAs, and lncRNAs. Sixteen significant triplets were revealed, in some of which, e.g., OIP5-AS1–miR-203a–c-MET and OIP5-AS1–miR-203a–ZEB2, both lncRNA and mRNA had sites for miR-203a direct binding. Transfection of the OVCAR-3 and SKOV-3 cell lines with the miR-203a mimic was used to confirm the novel links of miR-203a with ZEB2 and c-MET in OC. These connections suggest that the interactomes have the potential for diagnostics of metastasis at early onset.

HOXB13 induced LncRNA CYTOR aggravates spinal cord injury induced neuropathic pain via upregulating TJP1

“…lncRNA has been reported to involve in chromatin and genomic structural remodeling, RNA stabilization and transcriptional regulation, protein degradation [20][21][22]. While the vast majority mechanism investigations lead to the lncRNA/miRNA/mRNA axis, by which lncRNA transcriptionally regulates gene expression through acting as a molecular sponge for miRNA [23][24][25][26]. Herein, after our study validated the expression and biological functions of CYTOR in NP, we investigated the molecular mechanisms of CYTOR through identifying its downstream miRNA/mRNA axis.…”

The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential

“…Circ_0004390 (also known as circ-LPAR3) has been found to be significantly elevated in OC tissue and is believed to have a key role in OC cell proliferation [ 104 , 105 ]. Circ_0004390 might serve as a sponge for miR-198, so that overexpression of circ_0004390 could downregulate the expression of miR-198.…”

miR‐203a—A multifaceted regulator modulating cancer hallmarks and therapy response

“…128 In silico analysis by Zu et al and Pronina et al shows that DLGAP1-AS1/miR-203a-3p/THBS2 axis acts as a promising ceRNA regulatory network for the prognosis of GC 129 and OIP5-AS1-miR-203a-c-MET/ZEB2 axis as a potential regulator for OC progression and metastasis. 130 6 | CONCLUSION Among the regulatory ncRNAs, miRNAs are the key players in the altered expression of tumor suppressors as well as oncogenes. In addition to these, dysregulation of miRNA expression has a strong correlation with cell proliferation, migration, invasion, EMT, and acquired chemoresistance.…”

“…In NSCLC, increased expression of LINC00342 significantly increases the oncogenicity of cancer cells through the miR‐203a‐3p axis 128 . In silico analysis by Zu et al and Pronina et al shows that DLGAP1‐AS1/miR‐203a‐3p/THBS2 axis acts as a promising ceRNA regulatory network for the prognosis of GC 129 and OIP5‐AS1–miR‐203a–c‐MET/ZEB2 axis as a potential regulator for OC progression and metastasis 130 …”