Abstract
Accumulating evidence indicates that KIAA1199 plays a vital role in tumor progression. However, the role of KIAA1199 in hepatocellular carcinoma (HCC) still remains unknown. In this study, we found that KIAA1199 was upregulated in human HCC tissues and in highly metastatic HCC cell lines. Furthermore, the expression of KIAA1199 was significantly correlated with tumor size and metastasis in HCC. Knockdown of KIAA1199 inhibited cell proliferation and migration in vitro, and suppressed tumorigenicity and lung metastasis in vivo. In addition, silencing of KIAA1199 induced G1 phase arrest by reducing cyclinD1 expression. Moreover, KIAA1199 knockdown induced apoptosis by activating endoplasmic reticulum (ER) stress, which was based on the upregulation of ER stress markers, activating transcription factor 4 (ATF4) and CAAT/enhancer-binding protein homologous protein (CHOP). In conclusion, our data demonstrated that KIAA1199 knockdown inhibited the growth and metastasis of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide[1]
Further analysis of the clinicopathological characteristics in HCC samples showed that KIAA1199 overexpression positively correlated with tumor size (P = 0.043) and metastasis (P = 0.023), but no significant differences were observed with respect to age, sex, tumor number, and the alpha-fetoprotein (AFP) level (Table 1)
In accord with the results from tissues, we found that KIAA1199 was overexpressed in highly invasive HCC cell lines and hardly any in the normal liver cell line (Fig. 1c, d)
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide[1]. More than 90% of cancer-related deaths are the consequence of the tumor cells escaped from primary tumor to form metastases[2]. Genetic and epigenetic alterations are well characterized in HCC, the molecular pathogenesis still remains largely unknown[3]. Additional studies must be carried out to gain a better understanding of HCC progression in order to develop novel therapeutic targets. KIAA1199 was first identified as an inner ear-specific protein, which is located on chromosome band 15q25.14. It has been reported that KIAA1199 is upregulated in many types of tumors, such as colorectal cancer, gastric cancer, and breast cancer[5,6,7]. High levels of KIAA1199 were correlated with worse five-year survival
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