The Identification and Analysis of mRNA–lncRNA–miRNA Cliques From the Integrative Network of Ovarian Cancer

Abstract

Ovarian cancer is one of the leading causes of cancer mortality in women. Since little clinical symptoms were shown in the early period of ovarian cancer, most patients were found in phases III–IV or with abdominal metastasis when diagnosed. The lack of effective early diagnosis biomarkers makes ovarian cancer difficult to screen. However, in essence, the fundamental problem is we know very little about the regulatory mechanisms during tumorigenesis of ovarian cancer. There are emerging regulatory factors, such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), which have played important roles in cancers. Therefore, we analyzed the RNA-seq profiles of 407 ovarian cancer patients. An integrative network of 20,424 coding RNAs (mRNAs), 10,412 lncRNAs, and 742 miRNAs were construed with variance inflation factor (VIF) regression method. The mRNA–lncRNA–miRNA cliques were identified from the network and analyzed. Such promising cliques showed significant correlations with survival and stage of ovarian cancer and characterized the complex sponge regulatory mechanism, suggesting their contributions to tumorigenicity. Our results provided novel insights of the regulatory mechanisms among mRNAs, lncRNAs, and miRNAs and highlighted several promising regulators for ovarian cancer detection and treatment.

LncRNAs in Ovarian Cancer Progression, Metastasis, and Main Pathways: ceRNA and Alternative Mechanisms

“…However, direct lncRNA interactions with protein or mRNA are also observed, for example, WDR7-7 lncRNA with mRNA of the GPR30 gene [ 17 ]. Moreover, large-scale regulatory networks have already been outlined for lncRNA, mRNA, and miRNA in cancer cells [ 18 , 19 , 20 ]. LncRNAs add new layers to regulatory networks and deepen our understanding of the mechanisms of oncogenesis, which is necessary for a constructive approach to diagnosis, prognosis on cancer progression, response to therapy, as well as for the search for new therapeutic drugs.…”

<p>LEMD1-AS1 Suppresses Ovarian Cancer Progression Through Regulating miR-183-5p/TP53 Axis</p>

“…Previous studies have revealed that lncRNAs serve as miRNAs spongers in implication in OC. [19][20][21] miRNAs could be putative oncogenic or tumor-suppressive factors by acting as key modulators of gene expression, and are important targets of lncRNAs. 22,23 The putative miRNA targets of LEMD1-AS1 were then investigated in the present study.…”

Regulation Networks Driving Vasculogenic Mimicry in Solid Tumors

“…Created with Biorender.com. (104,105). This network promotes the acquisition of cellular phenotypes such as migration, invasion, angiogenesis, and VM (Figure 3).…”