From biomarkers to therapeutic targets—the promises and perils of long non-coding RNAs in cancer

Abstract

Biomarker-driven personalized cancer therapy is a field of growing interest, and several molecular tests have been developed to detect biomarkers that predict, e.g., response of cancers to particular therapies. Identification of these molecules and understanding their molecular mechanisms is important for cancer prognosis and the development of therapeutics for late stage diseases. In the past, significant efforts have been placed on the discovery of protein or DNA-based biomarkers while only recently the class of long non-coding RNA (lncRNA) has emerged as a new category of biomarker. The mammalian genome is pervasively transcribed yielding a vast amount of non-protein-coding RNAs including lncRNAs. Hence, these transcripts represent a rich source of information that has the potential to significantly contribute to precision medicine in the future. Importantly, many lncRNAs are differentially expressed in carcinomas and they are emerging as potent regulators of tumor progression and metastasis. Here, we will highlight prime examples of lncRNAs that serve as marker for cancer progression or therapy response and which might represent promising therapeutic targets. Furthermore, we will introduce lncRNA targeting tools and strategies, and we will discuss potential pitfalls in translating these into clinical trials.

Non-Coding microRNAs as Novel Potential Tumor Markers in Testicular Cancer

“…This group of RNAs has an average length of 22 nucleotides that do not code for proteins (non-coding RNA). miRNAs attach mRNAs by complementary base binding and can post-translationally control the expression of proteins in cells [12,40]. miRNAs affect a variety of molecular processes and are necessary for the proper development of tissues, drug resistance and immune response [41][42][43][44].…”

Depletion of LncRNA NEAT1 Rescues Mitochondrial Dysfunction Through NEDD4L-Dependent PINK1 Degradation in Animal Models of Alzheimer’s Disease

“…Emerging evidence has demonstrated that lncRNAs represent a novel class of pivotal regulators of gene functions and multiple physiological events (Wang et al, 2018(Wang et al, , 2019Yamazaki et al, 2018). They have been found to maintain sub-cellular architecture, stabilize protein complex, and participate in multiple biological processes (Del Vecchio et al, 2018;Gutschner et al, 2018;Liu et al, 2018;Wang et al, 2019;Yan et al, 2019;Yu et al, 2019). First discovered in 2007, nuclear enriched abundant transcript 1 (NEAT1) plays crucial roles both in carcinogenesis (Klec et al, 2019) and non-cancerous diseases, such as neurodegeneration and inflammation (Prinz et al, 2019).…”

Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8

“…Long noncoding RNA (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides and have been reported to participate in a variety of biological processes,including regulation of gene expression, subcellular architecture, and stabilization of protein complexes 3 . Mechanistically, lncRNAs sponge many different types of miRNAs, acting as competing endogenous RNAs (ceRNAs) to display its function.…”