miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition

Abstract

Background: Hepatocellular carcinoma (HCC) is a primary aggressive gastrointestinal neoplasm that affects patients worldwide. It has been shown that Wilms' tumor 1-associating protein (WTAP) is frequently upregulated in various cancers. However, the potential role of WTAP in HCC remains largely unknown.Methods: The expression levels of WTAP in human HCC tissues were determined by the western blotting and immunohistochemical (IHC) staining. A correlation between the WTAP expression, clinicopathological features, and the HCC prognosis was analyzed. The WTAP expression was silenced by short hairpin RNA (shRNA), and effects of the knockdown of WTAP on the proliferation and invasion of HCC cells were assessed. The microRNAs (miRNAs) involved in the regulation of the WTAP expression were identified by a bioinformatics analysis and further confirmed by in vitro assays.Results: The expression levels of WTAP in liver cancer tissues were significantly elevated and compared with those in the adjacent normal tissues and significantly correlated with the clinical stage and prognosis in patients with HCC. Further investigation revealed that the knockdown of WTAP drastically suppressed HCC cell proliferation and invasion abilities. Luciferase reporter assay and validation experiments confirmed that WTAP was a direct target of miR-139-5p. Moreover, the overexpression of WTAP could partly abolish the inhibitory effects of miR-139-5p on the HCC cell growth and invasion. Mechanistically, we revealed that the miR-139-5p/WTAP axis regulated the HCC progression by controlling the epithelial to mesenchymal transition (EMT).Conclusions: In summary, the results indicate that WTAP is a potential oncogene in HCC and miR-139-5p negatively regulates the WTAP expression. MiR-139-5p/WTAP can be utilized as a potential therapeutic target for HCC.

N6-Methyladenosine Modification Participates in the Progression of Hepatitis B Virus-Related Liver Fibrosis by Regulating Immune Cell Infiltration

“…WTAP was more expressed in gene clusterB than in gene clusterA and positively associated to the NKT cell infiltration in gene clusterB and in overall trend ( Figure 4D ; Supplementary Figure 1G ). WTAP was reported to improve the HCC progression ( 41 , 42 ). Taken together, these findings suggest a role for WTAP interacting with NKT cells in the progress of HBV-related liver fibrosis.…”

MicroRNA‐501‐3p inhibits the proliferation of kidney cancer cells by targeting WTAP

“…In hepatocellular carcinoma, the miR‐139‐5p loss‐mediated WTAP activation contributes to its progression. 36 Long noncoding RNA DUXAP8 promotes pancreatic carcinoma progression via the miR‐448/WTAP/Fak signaling axis 37 and miR‐155 accelerates the growth of human liver cancer cells by activating CDK2 via targeting H3F3A . 38 In addition, miR‐200c targets CDK2 and suppresses tumorigenesis in RCC.…”

Correlations between P2RX1 Expression and Gastrointestinal Cancers Prognosis and Immune Infiltration Based on Bioinformatics Analysis

“…Moreover, P2RX1 was noted to be associated with Wilms' tumor 1 associated protein (WTAP) in LIHC. WTAP often acts as an oncogene, and it is associated with the prognosis of patients with LIHC [21] . The positive association between the expression of P2RX1 and WTAP in this research promotes the inference of the probability that WTAP induces m6A modification on the mRNA of P2RX1 and coordinates with positive-readers or it links to the 3' UTR or 5' UTR of P2RX1 mRNA, accelerating the stability of P2RX1 mRNA.…”