Transcription factor Oct4 promotes osteosarcoma by regulating lncRNA AK055347

Abstract

Abstract. Osteosarcoma is the most common primary bone tumor in children and adolescents, typically presenting with a poor prognosis. Octamer-binding transcription factor 4 (Oct4) protein, encoded by the POU class 5 homeobox 1 gene, is important in maintaining self-renewal of pluripotent stem cells, and is closely associated with cancer. However, its role in osteosarcoma remains to be elucidated. The present study observed Oct4 was markedly increased in osteosarcoma cell lines and in human osteosarcoma tissue samples. Following Oct4 downregulation by small interfering RNA (siRNA) in osteosarcoma F5M2 cells, the cells exhibited significant decreases in proliferation and invasion ability, and an increase in cell apoptosis. Notably, downregulation of Oct4 decreased the expression of AK055347, a newly identified long noncoding RNA (lncRNA) in human tissues. The downregulation of AK055347 by siRNA resulted in a significant suppressive effect on proliferative and invasive ability, and promotion of cell apoptosis in osteosarcoma cells. Thus, the current study suggests Oct4 exerts a promoting effect in osteosarcoma, and identifies a novel lncRNA in osteosarcoma progression.

The Na+/K+ ATPase Inhibitor Ouabain Attenuates Stemness and Chemoresistance of Osteosarcoma Cells

“…Consistent with the above, in OS progression, sox2 is required for tumor development and cell proliferation and knockdown of sox2 inhibits OS cell migration and invasion [19]. Additionally, Oct4 promotes OS progression through regulating lncRNA AK055347 expression [20]. However, a recent work indicates that silencing of these master stemness regulators (Oct4, Sox2, Klf4, c-Myc, or Nanog) is insufficient to avoid the formation of teratomas, but can affect their differentiation potential [21], meaning that different stemness regulators might have different roles in different tumors by different mechanisms.…”

The long noncoding RNA cancer susceptibility candidate 2 inhibits tumor progression in osteosarcoma

“…Despite progress in cancer-associated research, the exact underlying molecular mechanisms of OS occurrence and development remain poorly understood. Numerous efforts have been made to establishing an association between lncRNA expression and tumor development (11,(26)(27)(28). Owing to the complexity of the tumor microenvironment, lncRNA may serve diverse roles in carcinogenesis based on tumor type.…”

The Role and Specific Mechanism of OCT4 in Cancer Stem Cells: A Review

“…The ability of MALAT1 to maintain the stemness of human colon CSCs may be achieved by targeted inhibition of miR-20b-5p and reducing the binding of miR-20b-5p to OCT4 mRNA (Pou5f1) ( 47 ). OCT4 promotes the invasion and proliferation of cancer cells by regulating the level of lncRNA AK055347 in human osteosarcoma cells ( 48 ). The activation of lncRNA AK028326 was also found to be directly regulated by Oct4 in mESCs ( 9 ).…”