Long noncoding RNAs: new insights into non-small cell lung cancer biology, diagnosis and therapy

Abstract

Recent advances in tiling array and high throughput analyses revealed that at least 87.3 % of the human genome is actively transcribed, though <3 % of the human genome encodes proteins. This unexpected truth suggests that most of the transcriptome is constituted by noncoding RNA. Among them, high-resolution microarray and massively parallel sequencing analyses identified long noncoding RNAs (lncRNAs) as nonprotein-coding transcripts. lncRNAs are largely polyadenylated and >200 nucleotides in length transcripts, involved in gene expression through epigenetic and transcriptional regulation, splicing, imprinting and subcellular transport. Although lncRNAs functions are largely uncharacterized, accumulating data indicate that they are involved in fundamental biological functions. Conversely, their dysregulation has increasingly been recognized to contribute to the development and progression of several human malignancies, especially lung cancer, which represents the leading cause of cancer-related deaths worldwide. We conducted a comprehensive review of the published literature focusing on lncRNAs function and disruption in nonsmall cell lung cancer biology, also highlighting their value as biomarkers and potential therapeutic targets. lncRNAs are involved in NSCLC pathogenesis, modulating fundamental cellular processes such as proliferation, cell growth, apoptosis, migration, stem cell maintenance and epithelial to mesenchymal transition, also serving as signaling transducers, molecular decoys and scaffolds. Also, lncRNAs represent very promising biomarkers in early-stage NSCLC patients and may become particularly useful in noninvasive screening protocols. lncRNAs may be used as predictive biomarkers for chemotherapy and targeted therapies sensitivity. Furthermore, selectively targeting oncogenic lncRNAs could provide a new therapeutic tool in treating NSCLC patients. lncRNAs disruption plays a pivotal role in NSCLC development and progression. These molecules also serve as diagnostic, prognostic and predictive biomarkers. Characterization of lncRNA genes and their mechanisms of action will enable us to develop a more comprehensive clinical approach, with the final goal to benefit our patients.

Knockdown of long non-coding RNA CCAT2 suppressed proliferation and migration of glioma cells

“…Moreover, accumulating studies have demonstrated the aberrant expression of lncRNAs in various human tumors, including colorectal cancer [17], liver cancer [18], breast cancer [19]and lung cancer [20]. For instance, lncRNA HOTAIR (Hox transcript antisense intergenic RNA) controls gene expression by interacting with a Polycomb Repressive Complex 2 (PRC2) and high levels of HOTAIR expression was investigated in multiple tumors pathogenesis and progression [21–23].…”

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-&alpha;-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

“…The EMT plays an important role in the invasion and metastasis of tumors. 57 The process is characterized by the loss of polarity and connectivity between epithelial cells and the acquisition of an interstitial cell phenotype under the influence of numerous factors. 58 During this process, mesenchymal markers such as N-cadherin are upregulated, and adhesion molecules such as E-cadherin are downregulated.…”

Increased Expression of Long Non-Coding RNA BCAR4 Is Predictive of Poor Prognosis in Patients with Non-Small Cell Lung Cancer

“…Recently, accumulating evidence has suggested that lncRNAs play a critical role in the regulation of cell proliferation and apoptosis, differentiation and development, as well as cancer development and progression (Taylor et al 2015;Ricciuti et al 2016). For instance, lncRNA MVIH was found to be significantly upregulated in breast cancer tissues than in adjacent noncancerous tissues, and patients with high MVIH levels showed poor overall survival and disease-free survival (Lei et al 2016).…”

“…In recent years, accumulating evidence has demonstrated that lncRNAs participate in the regulation of various biological processes, such as cell proliferation, differentiation, apoptosis, motility and so forth (Li and Hu 2015;Ricciuti et al 2016). Although lncRNAs are not translated into proteins, they can regulate the expression of oncogenes or tumor suppressors to control the tumorigenesis and cancer progression (Silva et al 2015).…”