Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A) modified circRNA, circNSUN2, frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly, N6-methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and HMGA2 are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that N6-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease.

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Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). However, the role of lncRNA in CRC liver metastasis remains unclear. Methods: a microarray was performed to identify the differentially expressed lncRNAs between CRC tissues with and without liver metastasis. Survival analysis was evaluated using the Kaplan-Meier method and assessed using the log-rank test. In vitro and in vivo assays were preformed to explore the biological effects of the differentially expressed lncRNA in CRC cells. Results: the lncRNA UICLM (up-regulated in colorectal cancer liver metastasis) was significantly up-regulated in cases of CRC with liver metastasis. Moreover, UICLM expression was higher in CRC tissues than in normal tissues, and UICLM expression was associated with poor patient survival. Knockdown of UICLM inhibited CRC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and liver metastasis in vivo. Ectopic expression of UICLM promoted CRC cell proliferation and invasion. Mechanistic investigations revealed that UICLM induced its biological effects by regulating ZEB2, as the oncogenesis facilitated by UICLM was inhibited by ZEB2 depletion. Further study indicated that UICLM acted as a competing endogenous RNA (ceRNA) for miR-215 to regulate ZEB2 expression. Conclusions: taken together, our findings demonstrate how UICLM induces CRC liver metastasis and may offer a novel prognostic marker and therapeutic target for this disease.

As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.