Recent studies show that YTH domain family 2 (YTHDF2) preferentially binds to m⁶A-containing mRNA regulates localization and stability of the bound mRNA. However, the role of YTHDF2 in pancreatic cancers remains to be elucidated. Here, we find that YTHDF2 expression is up-regulated in pancreatic cancer tissues compared with normal tissues at both mRNA and protein levels, and is higher in clinical patients with later stages of pancreatic cancer, indicating that YTHDF2 possesses potential clinical significance for diagnosis and prognosis of pancreatic cancers. Furthermore, we find that YTHDF2 orchestrates two cellular processes: promotes proliferation and inhibits migration and invasion in pancreatic cancer cells, a phenomenon called “migration-proliferation dichotomy”, as well as epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. Furthermore, YTHDF2 knockdown significantly increases the total YAP expression, but inhibits TGF-β/Smad signaling, indicating that YTHDF2 regulates EMT probably via YAP signaling. In summary, all these findings suggest that YTHDF2 may be a new predictive biomarker of development of pancreatic cancer, but a serious consideration is needed to treat YTHDF2 as a target for pancreatic cancer.

Linc-RoR was originally identified to be a regulator for induced pluripotent stem cells in humans and it has also been implicated in tumorigenesis. However, the underlying mechanism of Linc-RoR-mediated gene expression in cancer is poorly understood. The present study demonstrates that Linc-RoR plays an oncogenic role in part through regulation of c-Myc expression. Linc-RoR knockout (KO) suppresses cell proliferation and tumor growth. In particular, Linc-RoR KO causes a significant decrease in c-Myc whereas re-expression of Linc-RoR in the KO cells restores the level of c-Myc. Mechanistically, Linc-RoR interacts with heterogeneous nuclear ribonucleoprotein (hnRNP) I and AU-rich element RNA-binding protein 1 (AUF1), respectively, with an opposite consequence to their interaction with c-Myc mRNA. While Linc-RoR is required for hnRNP I to bind to c-Myc mRNA, interaction of Linc-RoR with AUF1 inhibits AUF1 to bind to c-Myc mRNA. As a result, Linc-RoR may contribute to the increased stability of c-Myc mRNA. Although hnRNP I and AUF1 can interact with many RNA species and regulate their functions, with involvement of Linc-RoR they would be able to selectively regulate mRNA stability of specific genes such as c-Myc. Together, these results support a role for Linc-RoR in c-Myc expression in part by specifically enhancing its mRNA stability, leading to cell proliferation and tumorigenesis.

Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored.

Objective: The long non‐coding RNA zinc finger E‐box‐binding homeobox 1 antisense 1 (ZEB1‐AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1‐AS1 in colon adenocarcinoma (COAD).Methods: QRT‐PCR was used to detect the expression of ZEB1‐AS1, miR‐455‐3p and p21‐activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1‐AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull‐down assay were used to demonstrate the mechanism of ZEB1‐AS1. We further explore the role of ZEB1‐AS1 in vivo though xenograft tumour assay.Results: We found that ZEB1‐AS1 expression was significantly up‐regulated in COAD tissues, and high ZEB1‐AS1 level was correlated with the poor prognosis of COAD patients. MiR‐455‐3p plays an anti‐cancer role in COAD by targeting PAK2. We confirmed that ZEB1‐AS1 promotes PAK2 expression by sponging miR‐455‐3p, thus facilitating COAD cell growth and metastasis.Conclusions: To sum up, this result illustrates the novel molecular mechanism of ZEB1‐AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.