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Review
. 2020 Dec 19;12(12):3843.
doi: 10.3390/cancers12123843.

Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer

Laura Schwarzmueller  1   2 , Oscar Bril  1   2 , Louis Vermeulen  1   2 , Nicolas Léveillé  1   2
Affiliations
Review

Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer

Laura Schwarzmueller et al. Cancers (Basel). .

Abstract

Maintenance of the intestinal epithelium is dependent on the control of stem cell (SC) proliferation and differentiation. The fine regulation of these cellular processes requires a complex dynamic interplay between several signaling pathways, including Wnt, Notch, Hippo, EGF, Ephrin, and BMP/TGF-β. During the initiation and progression of colorectal cancer (CRC), key events, such as oncogenic mutations, influence these signaling pathways, and tilt the homeostatic balance towards proliferation and dedifferentiation. Therapeutic strategies to specifically target these deregulated signaling pathways are of particular interest. However, systemic blocking or activation of these pathways poses major risks for normal stem cell function and tissue homeostasis. Interestingly, long non-coding RNAs (lncRNAs) have recently emerged as potent regulators of key cellular processes often deregulated in cancer. Because of their exceptional tissue and tumor specificity, these regulatory RNAs represent attractive targets for cancer therapy. Here, we discuss how lncRNAs participate in the maintenance of intestinal homeostasis and how they can contribute to the deregulation of each signaling pathway in CRC. Finally, we describe currently available molecular tools to develop lncRNA-targeted cancer therapies.

Keywords: RNA-based therapeutics; colorectal cancer; lncRNAs.

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Conflict of interest statement

The authors declare no conflict of interest in the content of this publication.

Figures

Figure 1
Figure 1
Deregulated lncRNAs involved in signaling pathways governing crypt homeostasis. Schematic representation of lncRNAs implicated in Wnt (a), Notch (b), Hippo (c), EGF (d), EphB (e), and BMP/TGF-β (f) pathways. Relative mechanisms of action are displayed.
Figure 2
Figure 2
Strategies to interfere with oncogenic lncRNAs. (a) RNA interference. Short hairpin RNAs (shRNAs) are first processed by DICER, which removes the terminal loop to generate small interfering RNAs (siRNAs). These are further incorporated into the RNA-induced silencing (RISC) complex to mediate the degradation of complementary sequences. (b) Antisense oligonucleotides. ASOs catalyze the cleavage of their complementary target RNAs via the ribonuclease H in both the cytoplasm and the nucleus. (c) CRISPR interference. The dCas9-KRAB/gRNA complex mediates the epigenetic silencing of targeted genes. (d) CRISPR Cas13. Guided by a CRISPR-RNA (crRNA), the ribonuclease Cas13 catalyzes the cleavage of single stranded RNA.
See this image and copyright information in PMC

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