RNF43 overexpression attenuates the Wnt/β‑catenin signalling pathway to suppress tumour progression in cholangiocarcinoma

• DOI: 10.3892/ol.2021.13107
• Publication Date: 2021-10-21T07:25:27Z
• Authors: Norma Pangestu; Piyasiri Chueakwon; Krajang Talabnin; Juthamas Khiaowichit; Chutima Talabnin
• Keywords: AXIN2

RING finger protein 43 (RNF43) is a ubiquitin E3 ligase that negatively regulates Wnt/β-catenin signalling. Mutation, inactivation and downregulation of RNF43 in cholangiocarcinoma (CCA) are associated with less favourable prognosis. Since the functional role CCA has not yet been demonstrated, present study aimed to assess effect its overexpression mediating suppression via signalling pathway inhibition. Accordingly, was overexpressed, various malignant phenotypic changes studied, including cell proliferation, migration, chemotherapeutic sensitivity expression several target genes. Overexpression cell-line KKU-213B hindered activation signalling, evidenced by: i) Accumulation β-catenin cytoplasmic fraction known Wnt genes at mRNA level [AXIN2, survivin (BIRC5), CCND1, MMP-7, c-MYC ABCB1 (MDR1)]; ii) reduction proliferation; iii) significant decrease migration upregulation E-cadherin (CDH1); iv) N-cadherin (CDH2), MMP-2, MMP-7 MMP-9. In addition, increased 5-fluorouracil ABC transporter [including ABCC1 (MRP1)]. The current results demonstrate for Blocking nuclear translocation; subsequent (the latter being involved progression drug susceptibility). Therefore, findings suggest could serve tumour suppressive CCA.