The OCT4 pseudogene POU5F1B is amplified and promotes an aggressive phenotype in gastric cancer

Abstract

POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.

Gastric cancer and gene copy number variation: emerging cancer drivers for targeted therapy

“…96 The POU5F1B gene (POU domain class 5 transcription factor 1B, the OCT4 pseudogene), which is located on human chromosome 8q24 near MYC, 97 is frequently amplified in GC. Hayashi et al 98 detected that POU5F1B copy number is amplified and overexpressed in GC, and it also promotes tumorigenicity and tumor growth. Therefore, POU5F1B amplification seems to be a GCassociated event that has oncogenic roles.…”

Identification of driver copy number alterations in diverse cancer types and application in drug repositioning

“…For the 11 protein‐coding genes ( CDKN2A , CBL , GRB7 , HDAC4 , HRAS , MYC , POU5F1B , PIK3CD , RB1 , RPS6KA1 and ZBTB48 ) shared by at least five cancer types, except POU5F1B (also known as OCT4‐pg1), all 10 of the other drivers have been recorded as cancer genes in the databases of census, DriverDB, Bushman or TSGene. Many studies have reported aberrations in POU5F1B in cancer, such as in gastric and prostate cancer (Hayashi et al ., ; Kastler et al ., ). In Fig.…”

Risk of eighteen genome-wide association study-identified genetic variants for colorectal cancer and colorectal adenoma in Han Chinese

“…Overexpression of this gene has recently been reported in gastric cancer and it can promote tumor formation and growth in vivo [35]. But the association was not observed between POU5FIB expression and genotype of rs10505477 [36].…”