Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis

Abstract

Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis. Angiogenesis, the formation of new blood vessels, is crucial for a tumor to receive sufficient amounts of nutrients and oxygen and therefore, to grow and exceed in its size over the diameter of 2 mm. In this review, the regulatory mechanisms of lncRNAs are described, which influence tumor angiogenesis by directly or indirectly regulating oncogenic pathways, interacting with other transcripts such as microRNAs (miRNAs) or modulating the tumor microenvironment. Further, angiogenic lncRNAs occurring in several cancer types such as liver, gastrointestinal cancer, or brain tumors are summarized. Growing evidence on the influence of lncRNAs on tumor angiogenesis verified these transcripts as potential predictive or diagnostic biomarkers or therapeutic targets of anti-angiogenesis treatment. However, there are many unsolved questions left which are pointed out in this review, hence driving comprehensive research in this area is necessary to enable an effective use of lncRNAs as either therapeutic molecules or diagnostic targets in cancer.

The PARP Inhibitor Olaparib Modulates the Transcriptional Regulatory Networks of Long Non-Coding RNAs during Vasculogenic Mimicry

“…LncRNAs have been proposed as important regulators of tumor angiogenesis, affecting tumor-associated cells, oncogenic pathways or binding to other RNA transcripts [ 6 ]. For instance, lncRNA HIF2PUT acts as a direct upstream promoter inducing EPAS1 (HIF2A) expression in colorectal cancer and consequently increasing angiogenesis; another example is the lncRNA PVT1, which stabilizes STAT3 and therefore indirectly increases VEGF expression in gastric cancer [ 7 ].…”

Long Intergenic Non-Coding RNA LINC00885 Promotes Tumorigenesis of Cervical Cancer by Upregulating MACC1 Expression Through Serving as a Competitive Endogenous RNA for microRNA-432-5p

“…Recently, lncRNAs have attracted the attention of more and more researchers. 8 , 27 , 28 An increasing number of studies have reported that lncRNAs are dysregulated and are essential regulators and tumor facilitators in cervical cancer. 29 Hence, identifying the lncRNAs involved in cervical cancer and exploring their detailed roles will be beneficial for developing effective targets to guide cancer diagnosis, prevention, and treatment.…”

Long non‑coding RNA USP30‑AS1 aggravates the malignant progression of cervical cancer by sequestering microRNA‑299‑3p and thereby overexpressing PTP4A1

“…lncRNAs have been extensively studied and identified as novel modulators during carcinogenesis and cancer progression (10)(11)(12). The aberrant expression of lncRNAs has been widely discovered in human cancers, manifesting a close correlation with aggressive biological events (13)(14)(15). Several studies have demonstrated the crucial regulatory actions…”