RPL22L1 induction in colorectal cancer is associated with poor prognosis and 5-FU resistance
Fig 6
Rpl22L1 regulates the expression of DNA damage repair enzymes, MGMT and MLH1, which together with Rpl22L1 induction, contribute to poor prognosis.
A. Immunoblotting performed on extracts from Mode K cells stably expressing control or RPL22L1-HA reveals increased expression of MGMT, decreased expression of MLH1, and no effect on MSH2. Actin served as loading control. B. Knockdown of RPL22L1 in the HCT116 cell line leads to decreased expression of MGMT. Actin served as loading control. C. Representative images of IHC staining for RPL22L1, MLH1, and MSH2 for two RPL22L1 high CRC samples from our TMA. CRC-B13 lacks MLH1 expression and so is considered MSI, while CRC-H4 expresses both MLH1 and MSH2 and is considered MSS. Image magnification is indicated in the scale bar. D-F. Kaplan-Meier overall survival curves for patients containing or lacking alterations in (D) MGMT alone (amplification, copy number gain and mRNA upregulation; (E) Rpl22L1 or MGMT (amplification, copy number gain and upregulation; (F) Rpl22L1 (amplification, copy number gain and mRNA upregulation) or MLH1 (mutation and two-fold downregulation); (G) alterations in Rpl22L1, MGMT, or MLH1. These combinations of alterations are associated with poor overall survival in the colorectal adenocarcinoma TCGA provisional data relative to patients lacking them. Web links to the TCGA data are embedded in the figure panels.