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.
Liu
Jian-Jun
JJ
Department of Physiology, Faculty of Medicine, National University of Singapore, Singapore.
Huang
Bao Hua
BH
Zhang
Jinqiu
J
Carson
Daniel D
DD
Hooi
Shing Chuan
SC
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