Using ncRNAs as Tools in Cancer Diagnosis and Treatment—The Way towards Personalized Medicine to Improve Patients’ Health

Abstract

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular network of crossed interactions (competing endogenous RNA networks, or ceRNET) that fine-tune the gene expression in both health and disease. The alteration of the equilibrium among such interactions can be enough to cause a transition from health to disease, but the opposite is equally true, leading to the possibility of intervening based on these mechanisms to cure human conditions. In this review, we summarize the present knowledge on these mechanisms, illustrating how they can be used for disease treatment, the current challenges and pitfalls, and the roles of environmental and lifestyle-related contributing factors, in addition to the ethical, legal, and social issues arising from their (improper) use.

MEIS1 Is a Common Transcription Repressor of the miR-23a and NORHA Axis in Granulosa Cells

“…In view of the core regulatory role of ncRNAs in some signal pathways and molecular regulatory networks controlling important physiological and pathological processes, these RNAs are regarded as molecular targets for the improvement of important economic traits in domestic animals [ 12 , 30 ], even potential markers for tumor diagnosis, and potential non-hormone drugs for disease treatment in humans [ 31 , 32 ]. Interestingly, both MEIS1 and NORHA were discovered to be located within the quantitative trait loci (QTLs) for sow fertility traits [ 33 , 34 ], a class of economically important traits in pig production.…”

An overview of natural products that modulate the expression of non-coding RNAs involved in oxidative stress and inflammation-associated disorders

“…Based on their chemical structures, phytochemicals are grouped into the following; phenols and polyphenols (e.g., quercetin, luteolin, genistein, resveratrol, calycosine, daidzein, and genistein), nitrogen-containing alkaloids (e.g., berberine and sanguinarine), terpenes (e.g., betulin), and sulfur compounds (e.g., sulforaphane) ( Yang et al, 2019 ) ( Table 2 ). Several studies especially on cancers have highlighted natural products in the modulation of oxidative stress and inflammatory disorders through their action on ncRNAs ( Saghafi et al, 2019 ; Irshad and Husain, 2021 ; Kalhori et al, 2021 ; Piergentili et al, 2022 ) but more research to unveil their in-depth mechanism of action is warranted as well as their investigation in other oxidative stress and inflammatory disorders. This review has been able to outline some of these natural products and present a brief summary in Table 3 .…”

“…The anticancerous effects of curcumin are portrayed by its ability to influence multiple signaling pathways like the NF-kB, MAPK, PTEN, and p53 which are all involved in the progression of cancers. For instance, curcumin inhibits progression and promotes cancer cell apoptosis by negatively modulating the lncRNA UCA1 ( Wang R. et al, 2018 ), it also upregulates microRNAs such as miR-502c, miR-181b, miR-16, miR-15a, miR-146b-5p, and miR-132 while downregulating others like miR-19a, miR-19b ( Piergentili et al, 2022 ). In hepatocarcinoma cells, it suppresses the expression of lincROR and blocks the Wnt/B-catenin signaling pathway activation ( Shao et al, 2020 ) while another study demonstrates that it inhibits GAS5 expression in lung cancer by affecting major pathways such as NF-kB and STAT3 ( De Bacco et al, 2011 ).…”

“…Plants containing this natural product include; green tea, red wine, and onions. It is commonly used but not limited to the treatment of heart conditions, diabetes, obesity, and certain cancers where they have been found to dysregulate miR-16, miR-145, MALAT-1, miR-155, miR-146a, miR-197, lncRNA SNHG7 and miR-223 ( Piergentili et al, 2022 ). Studies have demonstrated that quercetin has a protective effect against free radicals from smoking and lowers lncRNA DBH-AS1 expression through antioxidant activities in hepatocellular carcinoma ( Saghafi et al, 2019 ).…”

“…It also downregulates miR-34a in prostate cancer. It has also been widely researched in their modulation of ncRNAs in cancers like miR-151, miR-221, miR-222, miR-223 downregulation and miR-34a, miR-573-3p, miR-1296 upregulation in prostate cancers, miR-155 suppression in breast cancers, miR-34a, miR-200 upregulation in pancreatic cancer ( Piergentili et al, 2022 ).…”