Abstract
Hepatocyte nuclear factor 4 alpha (HNF4A) is a transcriptional factor which plays an important role in the development of the liver, kidney, and intestines. Nevertheless, its role in cervical cancer and the underlying mechanism remain unknown. In this study, both immunohistochemistry and western blotting revealed that the expression of HNF4A was downregulated in cervical cancer. Xenograft assays suggested that HN4A could inhibit tumorigenic potential of cervical cancer in vivo. Functional studies illustrated that HNF4A also inhibited the proliferation and viability of cervical cancer cells in vitro. In addition, FACS analysis implied that HNF4A could induce cell cycle arrest from the G0/G1 phase to S phase. Further studies suggested that HNF4A downregulated the activity of the Wnt/β-catenin pathway. Altogether, our data demonstrated that HNF4A inhibited tumor formation and proliferation of cervical cancer cells through suppressing the activity of the Wnt/β-catenin pathway.
Highlights
Cervical cancer is the fourth most common morbidity and mortality cancer in women worldwide in the latest epidemiological survey on cancers and is the second most common killer cancer in women after breast cancer [1]
The results showed that the Hepatocyte nuclear factor 4 alpha (HNF4A) protein was mainly expressed in the nucleus (Figure 1(a))
The results showed that the average relative expression of HNF4A in normal cervix (NC) was enormously higher than that in CC (Figure 1(e), 4:01 ± 1:535 vs. 0:4169 ± 0:1492, p < 0:001)
Summary
Cervical cancer is the fourth most common morbidity and mortality cancer in women worldwide in the latest epidemiological survey on cancers and is the second most common killer cancer in women after breast cancer [1]. Previous research in our laboratory has shown that a set of stem cell-related genes are involved in the pathogenesis of cervical cancer, such as LGR5 [5], OCT4 [6], NANOG [7], and SOX2 [8]. The Wnt/β-catenin signaling pathway plays important roles in various pathophysiological and physiological processes [9,10,11,12]. Activation of the Wnt/β-catenin signaling pathway has been reported in various cancers [13,14,15,16,17], including cervical cancer [18, 19]. Activation of the Wnt signaling pathway was considered an important process in the transformation of cervical precancerous lesions into cervical cancer [20, 21]
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