Long Non-coding RNAs and their Role in Metastasis

Abstract

Abstract.Metastasis is the major cause of death in patients with cancer. It is mediated by a multi-step process referred to as the metastatic cascade (1, 2). Initial steps include local invasion and migration, angiogenesis, epithelialmesenchymal transition (EMT) and intravasation. Tumor cells enter the circulation as single cells or circulating tumor cell clusters, are coated by platelets to escape an immune response and subsequently arrest in capillaries in distant organs as a prerequisite for extravasation. Colonization starts by homing of tumor cells in supporting niches of the organ parenchyma, followed by a latency phase which can last from several months to decades. A prerequiste for overt outgrowth of micrometastases is their adaptation to the local microenvironment and acquisition of colonisation-promoting traits (3-6). The pattern of colonized distant organs depends on the tumor type and can range from predominant spread to one organ and colonization of different types of organs sequentially or simultaneously (7). Several genes and their products have been identified to mediate crucial steps of the metastatic process such as metastasis initiation and progression, as well as organ-specific functions of metastasis (virulence) (8, 9). These gene products include proteases, chemokines, cytokines and their receptors, angiogenic factors, intracellular and transmembrane kinases, adhesion molecules, components of the extracellular matrix (ECM), GPI-linked receptors and carbohydrate metabolism-related enzymes (8, 9). More recently, an important impact of RNA-related molecules for metastasis has emerged. MicroRNAs (miRs) and other types of RNA modulate metastasis via regulatory networks (10,11). In this review we focus on the role of long non-coding RNAs (lncRNA) as promoters or inhibitors of metastasis in different tumor entities since there is an urgent need to define new targets for therapeutic intervention. With the exception of denosumab for treatment of bone metastases, all other agents evaluated in clinical studies for treatment of metastatic disease gave rise to mixed or disappointing results (6).

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…HOTAIR facilitates the HOXD gene cluster for transcriptional repression by recruiting PRC2 (Rinn, et al 2007). Analysis of data in the Cancer Genome Atlas (TCGA) revealed that increased HOTAIR expression correlates with metastasis and poor prognosis in breast and prostate cancers (Weidle, et al 2017). HOTAIR is both nuclear and cytoplasmic and considered an onco-lncRNA because of its ability to promote papillary thyroid cancer (PTC) cell proliferation and silencing its expression inhibited cell growth (Zhu, et al 2016).…”

“…Antisense oligonucleotides (ASO), liposome-delivered RNAi, vector-expressed shRNAs, and decoy RNAs or small molecules that compete for domain-domain interactions between lncRNA and proteins or within the lncRNA are of interest in targeting overexpressed lncRNAs in cancer (Weidle et al 2017). Targeting of lncRNAs using lncRNAs and nanoparticle-coated siRNAs has been successful in preclinical mouse models of BCa (Liu, et al 2015;).…”

“…Targeting of lncRNAs using lncRNAs and nanoparticle-coated siRNAs has been successful in preclinical mouse models of BCa (Liu, et al 2015;). Approximately 25 RNAi-based therapeutics are under clinical investigation (Weidle et al 2017). …”

LncRNA NKILA correlates with the malignant status and serves as a tumor‐suppressive role in rectal cancer

“…[7][8][9] Originally, NF-κB interacting lncRNA (NKILA) was found to be as a lncRNA mediated by NF-κB signaling pathway inducing inflammatory cytokines such as TNF-α and IL-1β in breast cancer cell. 11 However, the role of NKILA in rectal cancer was still unclear. 11 However, the role of NKILA in rectal cancer was still unclear.…”

Long non‐coding PANDAR as a novel biomarker in human cancer: A systematic review

“…3,4 Recent study showed non-coding RNAs (ncRNAs) are transcribed from non-protein-coding DNA sequences and key regulatory RNAs. 5 Long non-coding RNAs (LncRNAs) belong to ncRNAs that are longer than 200 nucleotides in length. 6 Previous studies suggested that the lncRNAs acted as transcriptional modulator, splicing regulator, post-transcriptional processor, enhancer, molecular decoys for miRNAs, chromatin remodeler, a guide for protein-protein, protein-DNA and protein-RNA interactions.…”