KIAA0101 Is Overexpressed, and Promotes Growth and Invasion in Adrenal Cancer

Abstract

BackgroundKIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm.Methodology/Principal FindingsKIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p<0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84% accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80% and invasion by 60% (p = 0.001; p = 0.006). We found no mutations in KIAA0101 in ACC.Conclusions/SignificanceKIAA0101 is overexpressed in ACC. Our data supports that KIAA0101 is a marker of cellular proliferation, promotes growth and invasion, and is a good diagnostic marker for distinguishing benign from malignant adrenocortical neoplasm.

Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma

“…We found that KIAA101 was significantly overexpressed at both the mRNA and protein levels in ccRCC, similarly to other cancers. In line with previous reports, we found that knockdown of KIAA0101 led to reduced migration and invasion ability of kidney cells but did not affect the cell proliferation similarly to adrenal cancer (31 ). In several cell types, proliferation and migration/invasion are distinct, supporting the "go or grow" hypothesis (32 ).…”

NS5ATP9 Suppresses Activation of Human Hepatic Stellate Cells, Possibly via Inhibition of Smad3/Phosphorylated-Smad3 Expression

“…Moreover, we proved that NS5ATP9 prevented LX-2 cells from proliferation and migration, and promoted apoptosis, which differs entirely from its proliferative and anti-apoptotic activities in most types of tumor cells [10,14,28,29], but is consistent with that in others, including HCC [30,31]. The promotion/suppression effects of NS5ATP9 on HSC apoptosis/proliferation may be one of the ways to protect HSCs from maintaining the activation status.…”

Expression of KIAA0101 protein is associated with poor survival of esophageal cancer patients and resistance to cisplatin treatment in vitro

“…(iii) Results of aCGH analysis revealed that KIAA0101 knockdown altered gene copy numbers, which could affect gene expression. These genes include MAPK, 15 BCL-2, 16 and MAL, 17 which has been shown in previous studies 10,13,14 to be altered in EC. In addition, several previously unreported genes (such as LY6K, MFAP5, HOXC9, TNFRSF12A, DHRS2, FST, and GPX3) were also found to be differentially expressed in KIAA0101-knocked-down esophageal cells, which warrants further investigation.…”

“…13 KIAA0101 enables tumor progression in several cancer types. 14 Our previous study showed that the KIAA0101 protein was elevated in gastric cancer tissues and promoted tumor cell proliferation, invasion, and served as a biomarker for prediction of early tumor recurrence. 10 However, earlier studies of KIAA0101 expression in EC did not reveal such a role of KIAA0101 in vitro or in vivo.…”