Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells.

Abstract

Dysregulation of protein synthesis is emerging as a major contributory factor in cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 (eukaryotic translation initiation factor 3) family, which is essential for initiation of protein synthesis in eukaryotic cells. Acquaintance with eIF3D is little since it has been identified as a dispensable subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in human colorectal cancers, indicating its importance for tumour progression. To further probe into its action in colon cancer, we utilized lentivirus-mediated RNA interference to knock down eIF3D expression in one colon cancer cell line HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell proliferation and colony formation in vitro. Flow cytometry analysis indicated that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic cells. Signalling pathways responsible for cell growth and apoptosis have also been found altered after eIF3D silencing, such as AMPKα (AMP-activated protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa], SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3β and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest that eIF3D might play an important role in colon cancer progression.

• Authors: Xiaojun Yu, Bo'an Zheng, Rui Chai
• Journal: Bioscience reports (Biosci Rep) Vol. 34 Issue 6 Pg. e00161 (Dec 12 2014) ISSN: 1573-4935 [Electronic] England
• PMID: 25370813 (Publication Type: Journal Article)

Chemical References

• BAD protein, human
• Eukaryotic Initiation Factor-3
• bcl-Associated Death Protein
• Poly(ADP-ribose) Polymerases
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• JNK Mitogen-Activated Protein Kinases
• Glycogen Synthase Kinase 3
• AMP-Activated Protein Kinases
• PRKAA1 protein, human

Topics

• AMP-Activated Protein Kinases
• Apoptosis (genetics)
• Blotting, Western
• Cell Proliferation (genetics)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Eukaryotic Initiation Factor-3 (genetics, metabolism)
• G1 Phase (genetics)
• G2 Phase Cell Cycle Checkpoints (genetics)
• Gene Expression Regulation, Neoplastic
• Genetic Vectors (genetics)
• Glycogen Synthase Kinase 3
• Glycogen Synthase Kinase 3 beta
• HCT116 Cells
• HEK293 Cells
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lentivirus (genetics)
• Poly(ADP-ribose) Polymerases (metabolism)
• RNA Interference
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (genetics)
• bcl-Associated Death Protein