Long non-coding RNAs: implications in targeted diagnoses, prognosis, and improved therapeutic strategies in human non- and triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) has been clinically difficult to manage because of tumor aggressiveness, cellular and histological heterogeneity, and molecular mechanisms’ complexity. All this in turn leads us to evaluate that tumor biological behavior is not yet fully understood. Additionally, the heterogeneity of tumor cells represents a great biomedicine challenge in terms of the complex molecular—genetical-transcriptional and epigenetical—mechanisms, which have not been fully elucidated on human solid tumors.Recently, human breast cancer, but specifically TNBC is under basic and clinical-oncology research in the discovery of new molecular biomarkers and/or therapeutic targets to improve treatment responses, as well as for seeking algorithms for patient stratification, seeking a positive impact in clinical-oncology outcomes and life quality on breast cancer patients.In this sense, important knowledge is emerging regarding several cancer molecular aberrations, including higher genetic mutational rates, LOH, CNV, chromosomal, and epigenetic alterations, as well as transcriptome aberrations in terms of the total gene-coding ribonucleic acids (RNAs), known as mRNAs, as well as non-coding RNA (ncRNA) sequences. In this regard, novel investigation fields have included microRNAs (miRNAs), as well as long ncRNAs (lncRNAs), which have been importantly related and are likely involved in the induction, promotion, progression, and/or clinical therapeutic response trackers of TNBC. Based on this, in general terms according with the five functional archetype classification, the lncRNAs may be involved in the regulation of several molecular mechanisms which include genetic expression, epigenetic, transcriptional, and/or post-transcriptional mechanisms, which are nowadays not totally understood.Here, we have reviewed the main dis-regulated and functionally non- and well-characterized lncRNAs and their likely involvement, from a molecular enrichment and mechanistic point of view, as tumor biomarkers for breast cancer and its specific histological subtype, TNBC. In reference to the abovementioned, it has been described that some lncRNA expression profiles correspond or are associated with the TNBC histological subtype, potentially granting their use for TNBC malignant progression, diagnosis, tumor clinical stage, and likely therapy. Based on this, lncRNAs have been proposed as potential biomarkers which might represent potential predictive tools in the differentiated breast carcinomas versus TNBC malignant disease. Finally, elucidation of the specific or multi-functional archetypal of lncRNAs in breast cancer and TNBC could be fundamental, as these molecular intermediary-regulator “lncRNAs” are widely involved in the genome expression, epigenome regulation, and transcriptional and post-transcriptional tumor biology, which in turn will probably represent a new prospect in clinical and/or therapeutic molecular targets for the oncological management of breast carcinomas in general and also for TNBC patients.

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

“…Numerous lncRNAs are reportedly upregulated in TNBCs and contribute to their aggressiveness [49,[116][117][118][119][120]. Zhang et al performed a detailed analysis of patient tumor RNA-seq data (TCGA) and revealed more than 50 lncRNAs that are upregulated in TNBCs/basal-like breast cancers; most of which are uncharacterized and represent potentially untapped targets in TNBC [121].…”

Correction to: Long non-coding RNAs: implications in targeted diagnoses, prognosis, and improved therapeutic strategies in human non- and triple-negative breast cancer

“…Upon publication of the original article [ 1 ], the authors noticed that the Figs. 1 , 2 and 3 were incorrectly given.…”

MicroRNAs' Gene Expression Technology for the Evaluation of Disease Modulation by Mild Nutrients

“…A biomarker is believed to be a characteristic indicator of normal biological processes, pathogenic processes, or pharmacological responses to therapeutic interventions [10,11]. In contrast, clinical endpoints are considered as variables representing a study subject's health from his/her perspective [12][13][14][15][16][17][18][19][20][21][22]. A variety of biomarkers exist today as surrogates to access clinical outcomes in diseases, predict the health of individuals, or improve drug development.…”