The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis

Abstract

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.

Keywords: cancer metastasis; colorectal cancer; lncRNAs; markers; signaling pathways; therapy.

Figure 1

LncRNAs regulate CRC metastasis by sponging miRNAs. (A) lncRNA LINC00668 promotes the metastasis and infiltration of CRC cells by sponging miR-188-5p and weakening its inhibiting effect on USP47 expression; (B) lncRNA MALAT1 regulates the miR-106b-5p expression by functioning as a competing endogenous RNA (ceRNA) and regulates the SLAIN2-associated microtubule mobility, leading to the CRC progression; (C) lncRNA TTTY15 functions as the ceRNA to regulate the expression of target gene DVL3 by sponging miR-29a-3p to promote CRC metastasis; (D) lncRNA-SNHG5 influences CRC cell metastasis by modulating the SNHG5/miR-132-3p/CERB5 axis. (E) lncRNA MIR4435-2HG acts as a ceRNA to promote the metastasis of CRC via upregulating YAP1 expression by sponging miR-206.

Figure 2

LncRNAs regulate CRC metastasis through protein binding. (A) lncRNA RPPH1 interacts with β-III tubulin (TUBB3) to prevent its ubiquitination and induces epithelial-mesenchymal transformation (EMT) of CRC; (B) lncRNA SNHG6 activates the endogenous colorectal cancer invasion pathway by down-regulating the expression of phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT)/rapamycin mechanical target (mTOR); (C) lncRNA SlCO4a1-AS1 stabilized β-catenin by impairing the interaction of β-catenin with GSKβ, thereby activating Wnt/β-catenin signaling in CRC cells; (D) lncRNA CASC11 promotes CRC cell proliferation and metastasis by interacting with hnRNP-K protein and activating the WNT/β-catenin signaling; (E) lncRNA RP11 is involved in the CRC development by forming the RP11/hnRNPA2B1/mRNA complex, which accelerates the mRNA degradation of two E3 ligases Siah1 and Fbxo45 and prevents the proteasomal degradation of Zeb1 to increase its nuclear accumulation.