Correction: The Tumor Suppressive Role of eIF3f and Its Function in Translation Inhibition and rRNA Degradation

Abstract

Deregulated translation plays an important role in human cancer. We previously reported decreased eukaryotic initiation factor 3 subunit f (eIF3f) expression in pancreatic cancer. Whether decreased eIF3f expression can transform normal epithelial cells is not known. In our current study, we found evidence that stable knockdown of eIF3f in normal human pancreatic ductal epithelial cells increased cell size, nuclear pleomorphism, cytokinesis defects, cell proliferation, clonogenicity, apoptotic resistance, migration, and formation of 3-dimensional irregular masses. Our findings support the tumor suppressive role of eIF3f in pancreatic cancer. Mechanistically, we found that eIF3f inhibited both cap-dependent and cap-independent translation. An increase in the ribosomal RNA (rRNA) level was suggested to promote the generation of cancer. The regulatory mechanism of rRNA degradation in mammals is not well understood. We demonstrated here that eIF3f promotes rRNA degradation through direct interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) K. We showed that hnRNP K is required for maintaining rRNA stability: under stress conditions, eIF3f dissociates hnRNP K from rRNA, thereby preventing it from protecting rRNA from degradation. We also demonstrated that rRNA degradation occurred in non-P body, non-stress granule cytoplasmic foci that contain eIF3f. Our findings established a new mechanism of rRNA decay regulation mediated by hnRNP K/eIF3f and suggest that the tumor suppressive function of eIF3f may link to impaired rRNA degradation and translation.

Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training

“…Indeed, eIF3f negatively regulates cell growth by inhibiting both cap-dependent and capindependent translation and by increasing rRNA degradation in cancer cells [160,161]. In this model, rRNA degradation is carried out by direct interaction between eIF3f and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a RNA-binding protein required for maintaining rRNA stability [161]. eIF3f interaction with hnRNP promotes hnRNP dissociation from rRNA leading to rRNA degradation [161].…”

“…In this model, rRNA degradation is carried out by direct interaction between eIF3f and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a RNA-binding protein required for maintaining rRNA stability [161]. eIF3f interaction with hnRNP promotes hnRNP dissociation from rRNA leading to rRNA degradation [161]. eIF3f also reduces tumor growth by interacting with the secretory heterodimeric glycoprotein clusterin and interrupting its anti-apoptotic property [162].…”

Functional Gene Clusters in Global Pathogenesis of Clear Cell Carcinoma of the Ovary Discovered by Integrated Analysis of Transcriptomes

“…In melanoma and pancreatic cancer, eIF3f was down-regulated, and the overexpression of eIF3f was noted to be associated with an inhibition of proliferation and an increased apoptosis in both pancreatic cancer and melanoma cell lines [57,58]. eIF3f can also interact with heterogeneous nuclear ribonucleoprotein (hnRNP) and induce rRNA degeneration, which can inhibit protein translation [59]. Furthermore, eIF3f can suppress Akt and ERK signaling, as well as stabilize p53 [60] In our data, eIF3f was also down-regulated, as is the case in melanoma and pancreatic cancer.…”