Repression of HIP/RPL29 expression induces differentiation in colon cancer cells.
We had previously shown that the expression of heparin/heparan sulfate interacting protein/ribosomal protein L29 (HIP/RPL29) was upregulated in colon cancer tissues. The present study investigated the role of HIP/RPL29 in differentiation in colon cancer cells. Inducing cellular differentiation in HT-29 cells by both sodium butyrate and glucose deprivation resulted in a significant downregulation of HIP/RPL29 expression. The beta-catenin/Tcf-4 pathway is the most important pathway controlling the switch between cellular differentiation and proliferation in intestinal epithelial cells. Inducing differentiation by dominant-negative inhibition of the beta-catenin/Tcf-4 complexes in LS174T cells also resulted in downregulation of HIP/RPL29. To determine whether a lower expression of HIP/RPL29 could induce differentiation in cancer cells, small interfering RNA (siRNA) targeting HIP/RPL29 was transfected into LS174T cells. The resultant knockdown of HIP/RPL29 expression induced cellular differentiation, as shown by the increased expression of two known markers of differentiation in LS174T cells, galectin-4 and mucin-2. In addition, the differentiation process induced by repression of HIP/RPL29 expression was accompanied by the upregulation of p21 and p53. In conclusion, HIP/RPL29 plays a role in the cellular differentiation process in colon cancer cells. The differentiation process is at least partially mediated by the upregulation of p21 and p53 pathways.
Department of Physiology, Faculty of Medicine, National University of Singapore, Singapore.
Jian-Jun
JJ
Liu
Bao Hua
BH
Huang
Jinqiu
J
Zhang
Daniel D
DD
Carson
Shing Chuan
SC
Hooi
D000469:Alkaline Phosphatase / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D037541:Galectin 4 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D055262:Mucin-2; D009077:Mucins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D015398:Signal Transduction / Q000502:physiology; D051820:TCF Transcription Factors / Q000235:genetics; D058118:Transcription Factor 7-Like 2 Protein; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors
D001779:Blood Coagulation Factors; D002087:Butyrates; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037541:Galectin 4; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C104946:RPL29 protein, human; D012269:Ribosomal Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D000469:Alkaline Phosphatase; D005947:Glucose