PBX3 is associated with proliferation and poor prognosis in patients with cervical cancer

Abstract

Pre-B-cell leukemia homeobox 3 (PBX3) is upregulated in various malignancies; however, the role of PBX3 in cervical cancer (CC) is unknown. The purpose of this study was to explore the expression characteristics, clinicopathological significance, and molecular biological function of PBX3 in CC. The expression levels of PBX3 were analyzed in CC cell lines and tumor specimens by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining. The clinicopathological characteristics associated with PBX3 expression were evaluated. An RNA interference approach was employed to suppress PBX3 expression in CC in vitro and in vivo, determine its role in cell proliferation and analyze its molecular function. We found that PBX3 expression was significantly upregulated in CC cell lines and clinical specimens compared with normal cells and adjacent nontumorous cervical tissues. PBX3 was an independent predictive factor of poor prognosis, and its expression was correlated with tumor diameter, pathological grading, lymph node metastasis, invasion depth, vascular invasion, and clinical stage of CC. Multivariate analysis suggested that PBX3 expression may represent an independent prognostic indicator of the survival of CC patients. CC patients with high PBX3 expression exhibited reduced overall survival compared with those with low PBX3 expression. Additionally, stable downregulation of PBX3 expression in CC cell lines suppressed cell proliferation and decreased p-AKT protein expression levels in vitro. Similarly, in vivo assays demonstrated that PBX3 downregulation in CC cells markedly inhibited tumor size and weight. Overall, we demonstrated that PBX3 can promote CC cell proliferation via the AKT signaling pathway and that it may serve as a prognostic marker. Our data indicate that inactivation of PBX3 may be an effective clinical treatment for CC.

Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis

“…PBX3 is highly expressed in a variety of cancer tissues, such as prostate and cervical cancer [14,16]. Han et al demonstrated that PBX3 expression is a critical determinant for maintaining the characteristics of tumorinitiating cells in hepatocellular carcinoma [17].…”

“…A recent study revealed that PBX3 is a critical regulatory protein of the epithelialmesenchymal transition (EMT) network in colorectal cancer [13]. Dysregulation of PBX3 expression has been observed in many cancer types, such as prostate, gastric, cervical, and liver cancer [14][15][16][17]. Nonetheless, the expression and function of PBX3 in LSCC are still unknown.…”

PBX3 in Cancer

“…In cervical cancer, PBX3 overexpression promotes proliferation through the AKT pathway, and high levels of expression in primary tumors are associated with a poor prognosis [57], and, as with the other cancers described above, PBX3 expression is suppressed by an miR, miR-526b, preventing cells from undergoing EMT [35].…”

“…Based on the above, it is becoming clear that PBX3 interacts principally with the MAPK, AKT, and WNT signaling pathways (Figure 1). PBX3 was shown to increase signaling through MEK/ERK in several studies [18,57,58], although to date the only component of the pathway shown to be directly upregulated by PBX3 is the tyrosine kinase receptor Flt3 [41]. Activation of this pathway represents a positive feedback loop in which increased expression of the Myc transcription factor activates LIN28 expression, which in turn inhibits biogenesis of miR-let-7b, an miR that blocks PBX3 expression post-transcriptionally [18].…”

Oncogenic and tumor suppressor function of MEIS and associated factors

“…The overexpression of NOTCH3 is correlated with the overexpression of Jagged-1 and Pbx1b in cervical SCCs, yet there is no established relationship between Pbx1b overexpression and patient survival (Yeasmin et al, 2010). PBX3 is overexpressed in the cytoplasm of cervical cancer cells and tissues and its expression is related to poor prognosis, tumor diameter, pathological grade, clinical stage lymph node metastasis, invasion depth, and vascular invasion (Li et al, 2017). The function of PBX3 is likely controlled by the AKT signaling pathway in cervical cancer (Li et al, 2017).…”