Open AccessO‐Glc NA c‐induced nuclear translocation of hn RNP ‐K is associated with progression and metastasis of cholangiocarcinoma
Author(s) -
Phoomak Chatchai,
Park Dayoung,
Silsirivanit Atit,
Sawanyawisuth Kanlayanee,
Vaeteewoottacharn Kulthida,
Detarya Marutpong,
Wongkham Chaisiri,
Lebrilla Carlito B.,
Wongkham Sopit
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12406
Subject(s) - microbiology and biotechnology , chemistry , rna , biology , biochemistry , gene
O‐Glc NA cylation is a key post‐translational modification that modifies the functions of proteins. Associations between O‐Glc NA cylation, shorter survival of cholangiocarcinoma ( CCA ) patients, and increased migration/invasion of CCA cell lines have been reported. However, the specific O‐Glc NA cylated proteins ( OGP s) that participate in promotion of CCA progression are poorly understood. OGP s were isolated from human CCA cell lines, KKU ‐213 and KKU ‐214, using a click chemistry‐based enzymatic labeling system, identified using LC ‐ MS / MS , and searched against an OGP database. From the proteomic analysis, a total of 21 OGP s related to cancer progression were identified, of which 12 have not been previously reported. Among these, hn RNP ‐K, a multifaceted RNA ‐ and DNA ‐binding protein known as a pre‐ mRNA ‐binding protein, was one of the most abundantly expressed, suggesting its involvement in CCA progression. O‐Glc NA cylation of hn RNP ‐K was further verified by anti‐ OGP /anti‐hn RNP ‐K immunoprecipitations and sWGA pull‐down assays. The perpetuation of CCA by hn RNP ‐K was evaluated using si RNA , which revealed modulation of cyclin D1, XIAP , EMT markers, and MMP 2 and MMP 7 expression. In native CCA cells, hn RNP ‐K was primarily localized in the nucleus; however, when O‐Glc NA cylation was suppressed, hn RNP ‐K was retained in the cytoplasm. These data signify an association between nuclear accumulation of hn RNP ‐K and the migratory capabilities of CCA cells. In human CCA tissues, expression of nuclear hn RNP ‐K was positively correlated with high O‐Glc NA cylation levels, metastatic stage, and shorter survival of CCA patients. This study demonstrates the significance of O‐Glc NA cylation on the nuclear translocation of hn RNP ‐K and its impact on the progression of CCA.