Overexpression of APC11 predicts worse survival in lung adenocarcinoma

Abstract

BackgroundAnaphase-promoting complex subunit 11 (APC11) plays an important role in gathering E2 and catalyzing ubiquitin-chain formation to support ubiquitination of substrates by acting as a catalytic core subunit of anaphase-promoting complex (APC/C). However, whether APC11 is implicated in the tumorigenesis of lung cancer is never known.Materials and methodsIn this study, we used an online survival analysis software to estimate the prognostic value of APC11 mRNA expression level for lung cancer. Cell Counting Kit-8 assay, colony-forming assay, and transwell assay were used to assess the biological functions of APC11 in lung cancer cells. Then, 107 lung cancer patient tissues were collected to examine the expression level of APC11 by immunohistochemistry staining. Kaplan–Meier method and univariate Cox regression analysis were performed to reveal the prognostic value of APC11 protein expression in lung cancer.ResultsHigher mRNA level of APC11 was significantly associated with worse survival for lung adenocarcinoma, but not for lung squamous cell carcinoma. Knockdown of APC11 by siRNA apparently inhibited cell proliferation and colon formation in both H1299 and H358 cells. In addition, silencing of APC11 decreased cell migrative and invasive abilities. Moreover, immunohistochemical analysis showed that APC11 was highly expressed in lung cancer tissues, and multivariate analysis suggested that APC11 overexpression was an independent prognostic factor in lung adenocarcinoma.ConclusionWe suggest that APC11 could serve as a prognostic biomarker and a novel target in treating lung adenocarcinoma.

The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase

“…Conversely, APC11 overexpression promoted cell proliferation and was associated with poorer prognosis. Collectively these findings show that APC11 crucially contributes to the development of lung adenocarcinoma (Zhou et al 2018). APC11 overexpression has also been reported in colorectal cancer cell lines, which significantly correlated with chromosomal instability, lymphovascular invasion and residual tumours (Drouet et al 2018).…”

“…Abnormally high expression levels of APC11 have been reported in lung cancer (Zhou et al 2018) where high APC11 messenger RNA (mRNA) levels significantly correlated with poorer overall survival for lung adenocarcinoma. siRNA knockdown of APC11 arrested cells in mitosis and significantly reduced cell proliferation, colony formation and migration and invasive capabilities.…”

Regulation of the anaphase promoting complex/cyclosome by the degradation of its unassembled catalytic subunit, Apc11

“…This balance may explain why only a fraction of cells overexpressing Apc11 cleaved Scc1. Nevertheless, the dire physiologic consequences of unregulated Apc11 are evident from 2 very recent studies that identified physiologic excess of Apc11 in colorectal cancer (44) and adenocarcinoma (45). In the first manuscript, different mRNA and protein expression analyses [quantitative real-time-PCR, Western blot, Tissue MicroArray (TMA) of 82 primary colorectal cancer tissues, and public datasets], revealed that the overexpression of APC11, but not of other APC/C subunits (APC2 and APC10), is significantly correlated with chromosomal instability.…”