Modulation of non-coding RNAs by resveratrol in ovarian cancer cells: In silico analysis and literature review of the anti-cancer pathways involved

Abstract

Background and aim Non-coding RNAs control cell functioning through affecting gene expression and translation and their dysregulation is associated with altered cell homeostasis and diseases, including cancer. Nutraceuticals with anti-cancer therapeutic potential have been shown to modulate non-coding RNAs expression that could impact on the expression of genes involved in the malignant phenotype. Experimental procedure Here, we report on the microarray profiling of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and on the associated biochemical pathways and functional processes potentially modulated in OVCAR-3 ovarian cancer cells exposed for 24 h to Resveratrol (RV), a nutraceutical that has been shown to inhibit carcinogenesis and cancer progression in a variety of human and animal models, both in vitro and in vivo . Diana tools and Gene Ontology (GO) pathway analyses along with Pubmed literature search were employed to identify the cellular processes possibly affected by the dysregulated miRNAs and lncRNAs. Results and conclusion The present data consistently support the contention that RV could exert anti-neoplastic activity via non-coding RNAs epigenetic modulation of the pathways governing cell homeostasis, cell proliferation, cell death and cell motility.

Novel long noncoding RNA LINC02323 promotes cell growth and migration of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p

“…According to the previous description, different lncRNAs can interact with specific miRNAs, and lncRNAs and miRNAs synergistically regulate various aspects of gene expression, thereby maintaining the balance of internal environment 17‐19 . miRNA sponge function has the unique characteristics as an ideal ceRNA 20 .…”

How Autophagy Shapes the Tumor Microenvironment in Ovarian Cancer

“…The haploinsufficient tumor suppressor gene BECN1 (that encodes for the protein BECLIN-1) has been the first autophagy gene that was found to predispose to OC development when monoallelically deleted (35,36). Autophagy in ovarian cancer is subjected to epigenetic regulation by histone de-acetylases (37), by hypomethylation (38), and by non-coding RNAs (39)(40)(41). Autophagy, being a stress response that can be regulated epigenetically, it is not surprising that the TME can modulate the actual level of autophagy in ovarian cancer cells (10).…”

Cyclodextrin nanosponge for the GSH-mediated delivery of Resveratrol in human cancer cells

“…The differential response elicited depends on the genetic/epigenetic and metabolic status of the cancer cells targeted, thus underling the need of a critical assessment of these features when designing theranostics for personalized cancer therapy 40 , 57 . Further, the benefits promoted by RV include the interruption of pro-inflammatory cross-talk occurring within the tumor microenvironment 18 , the inhibition of cancer cell migration 9 and the modulation of non-coding RNAs 10 . In addition, RV can act as caloric restriction mimetic and could substitute for restriction diet by sensitizing cancer cells to chemotherapy along with the reduction of related side effects 11 , 58 .…”

“…RV provides a wide range of preventive and therapeutic effects against different types of cancer, as testified by the increasing number of ongoing clinical trials that are screening its effectiveness as anti-cancer 5 . As a matter of fact, RV has shown the ability to reduce tumor growth in vivo 6 - 8 , and this anti-cancer activity has been linked to epigenetic mechanisms 9 , 10 , autophagy 11 - 13 , apoptosis 14 , 15 , induction of senescence 16 , 17 , interruption of the crosstalk between cancer cells and stromal fibroblasts 18 , among others. However, low aqueous solubility, chemical instability, and non-selectivity are the major limitations for the employment of RV in cancer therapy in humans 19 - 21 .…”