Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion

Abstract

Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

microRNA‑196b promotes cell migration and invasion by targeting FOXP2 in hepatocellular carcinoma

“…Accordingly, we suggest that miR-196b promotes tumor progression via exerting a pro-metastatic role in HCC. FOXP2 has been recognized as a tumor suppressor and suppresses the metastasis of HCC and breast cancer (15,28). Data from the GEO database further confirmed the underexpression of FOXP2 in HCC.…”

“…5D), which initially suggested that the miR-196b and 3'UTR of FOXP2 may combine with each other. A recent study found that FOXP2 was prominently reduced in HCC tissues and inhibited migration and invasion of cancer cells (15). Data from the GEO database (GSE45436) demonstrated that the expression of FOXP2 in HCC tissues was notably downregulated compared to that noted in normal liver tissues (P<0.0001, Fig.…”

High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin

“…Although the miR-122 mimic upregulated the cell proliferation, motility, and invasion activities, occludin knockdown only upregulated cell motility. Target prediction programs predict that putative miR-122 binding sequences exist in other genes involved in cell growth [e.g., p27 (36), PHD3 (37,38), and DUSP2 (39)] and invasion [e.g., CPEB1 (40), FOXP2 (41), and SOX17 (42)]. Occludin is known to mediate the MAPK signalling pathway via oncogenic proteins such as Raf (29).…”

Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

“…Numerous recent studies indicate a tumor suppressor like role for FOXP2 (Campbell et al, 2010;Cuiffo et al, 2014;Yan et al, 2015;Diao et al, 2018;Song et al, 2017;Li et al, 2019), others present evidence for an oncogene-like role of the protein (Campbell et al, 2010;Zhong et al, 2017;Wu et al, 2018;.…”