LncRNAs in Non-Small-Cell Lung Cancer

Abstract

<jats:p>Lung cancer is associated with a high mortality, with around 1.8 million deaths worldwide in 2018. Non-small-cell lung cancer (NSCLC) accounts for around 85% of cases and, despite improvement in the management of NSCLC, most patients are diagnosed at advanced stage and the five-year survival remains around 15%. This highlights a need to identify novel ways to treat the disease to reduce the burden of NSCLC. Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides in length which play important roles in gene expression and signaling pathways. Recently, lncRNAs were implicated in cancer, where their expression is dysregulated resulting in aberrant functions. LncRNAs were shown to function as both tumor suppressors and oncogenes in a variety of cancer types. Although there are a few well characterized lncRNAs in NSCLC, many lncRNAs remain un-characterized and their mechanisms of action largely unknown. LncRNAs have success as therapies in neurodegenerative diseases, and having a detailed understanding of their function in NSCLC may guide novel therapeutic approaches and strategies. This review discusses the role of lncRNAs in NSCLC tumorigenesis, highlighting their mechanisms of action and their clinical potential.</jats:p>

The Mechanistic Roles of ncRNAs in Promoting and Supporting Chemoresistance of Colorectal Cancer

“…They do not have an open reading frame, often harbor a poly-A tail, can be spliced, and are generally found in the cytoplasm and nucleus of a cell [46,65,67,68]. LncRNAs found in the nucleus are functionally involved in gene regulatory procedures, such as promoter specific repression or activation of transcription [34,[69][70][71] or epigenetic gene regulation [72,73] and those found in the cytoplasm modulate post-transcriptional gene regulatory processes [7,37,46,[74][75][76]. In addition, they modulate protein interactions, stability and affect their cellular localisation, together with controlling signalling cascades and any changes in gene expression [73].…”

“…LncRNAs found in the nucleus are functionally involved in gene regulatory procedures, such as promoter specific repression or activation of transcription [34,[69][70][71] or epigenetic gene regulation [72,73] and those found in the cytoplasm modulate post-transcriptional gene regulatory processes [7,37,46,[74][75][76]. In addition, they modulate protein interactions, stability and affect their cellular localisation, together with controlling signalling cascades and any changes in gene expression [73]. CircRNAs are a category of endogenous ncRNA molecules which are widely expressed in eukaryotic cells and exhibit both location-and step-specificity [77,78].…”

“…Despite their functional roles in cells, their biological roles remain largely speculative. Something common between both lncRNAs and circRNAs is that they can both act as miRNA sponges or competing endogenous RNAs (ceRNAs) to competitively bind to and sequester miRNAs, decreasing their regulatory effect on mRNAs [73,[86][87][88]. CeRNAs refers to different ncRNAs (e.g., circRNAs and lncRNAs) which compete (through interactions/crosstalk) for the same pool of miRNAs, thus in turn regulate the activity of miRNAs [89].…”

Long non‐coding RNA HCG11 sponging miR‐522‐3p inhibits the tumorigenesis of non‐small cell lung cancer by upregulating SOCS5

“…7 Current research suggests that the functional mechanism of lncRNA mainly includes the regulation of transcription, post-transcriptional regulation, protein transport and mRNA degradation. 8,9 Many studies have shown that lncRNAs can act as either tumor suppressors or promoters in the occurrence and development of NSCLC, such as PCNA-AS1 and FTX. 10,11 LncRNA HLA complex group 11 (HCG11) has been reported to be involved in human cancers.…”

Long Non-Coding RNAs in Diffuse Large B-Cell Lymphoma

“…As a result, lncRNAs regulate a broad range of biological processes, including aging, cell growth and differentiation, hematopoiesis, and immune response [ 8 , 9 , 10 , 11 ]. Accordingly, numerous studies have reported highly diverse roles for lncRNAs in cancer [ 12 , 13 , 14 ], including development and maintenance of resistance to anti-cancer therapy [ 15 , 16 , 17 , 18 ]. Most prominent examples involve well-characterized lncRNAs, such as CDKN2B antisense RNA 1 ( CDKN2B-AS1 , also known as ANRIL ) [ 19 ], growth arrest specific 5 ( GAS5 ) [ 20 , 21 ], H19 imprinted maternally expressed transcript ( H19 ) [ 22 , 23 ], HOX transcript antisense RNA ( HOTAIR ) [ 24 , 25 ], metastasis associated lung adenocarcinoma transcript 1 ( MALAT1 ) [ 26 , 27 ], and X inactive specific transcript ( XIST ) [ 28 , 29 ].…”