LncRNA BCAR4 promotes liver cancer progression by upregulating ANAPC11 expression through sponging miR­1261.

Liver cancer is a malignant tumor that occurs in the liver and can be divided into primary and secondary liver cancer. Long non­coding RNA (lncRNA) breast cancer anti­estrogen resistance 4 (BCAR4) has been demonstrated to promote the development of various types of cancer. However, the function of lncRNA BCAR4 in liver cancer remains unclear. In the present study, the expression of lncRNA BCAR4 was notably elevated in liver cancer compared with adjacent non­tumor tissues. Functional in vitro assays demonstrated that knockdown of lncRNA BCAR4 inhibited the proliferation, migration and invasion of Huh­7 cells. In addition, lncRNA BCAR4 was demonstrated to directly bind to microRNA (miR)­1261, and miR­1261 expression negatively correlated with the expression of lncRNA BCAR4. Through bioinformatics analysis, lncRNA BCAR4 was predicted to target anaphase­promoting complex subunit 11 (ANAPC11) through miR­1261. In addition, the results demonstrated that lncRNA BCAR4 increased the expression of ANAPC11 by inhibiting miR­1261 expression. Consistently, overexpression of ANAPC11 or inhibition of miR­1261 significantly rescued liver cancer cell proliferation induced by knockdown of lncRNA BCAR4. Collectively, the results of the present study demonstrated that lncRNA BCAR4 may promote liver cancer development by directly binding to miR­1261 and targeting ANAPC11.

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

One of the challenges encountered by the protein quality control machinery is the need to ensure that members of multiprotein complexes are available in the correct proportions. In this study, we demonstrate that the ubiquitin proteasome system (UPS) mediates the degradation of Apc11, the catalytic core subunit of the anaphase promoting complex/cyclosome (APC/C). In vitro studies have shown that Apc11, together with its E2 enzyme, is sufficient to ubiquitinate substrates independently of the APC/C. Here, we establish that this can occur in living yeast cells. We show that the tight controls regulating the function of the fully assembled APC/C can be circumvented when its substrates are ubiquitinated by the excess levels of Apc11 independently of the assembled complex. We thus suggest that the UPS-mediated degradation of Apc11 is an overlooked mechanism ensuring that proper function of the APC/C is limited to suitably delimited holoenzymes and that an imbalance in protein expression may result in detrimental gain-of-function activity, rather than merely the disruption of protein complex stoichiometry.-Volpe, M., Levinton, N., Rosenstein, N., Prag, G., Ben-Aroya, S. Regulation of the anaphase promoting complex/cyclosome by the degradation of its unassembled catalytic subunit, Apc11.

Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer.

After a diagnosis of colorectal cancer (CRC), approximately 50% of patients will present distant metastasis. Although significant progress has been made in treatments, most of them will die from the disease. We investigated the predictive and prognostic potential of APC11, the catalytic subunit of APC/C, which has never been examined in the context of CRC. The expression of APC11 was assessed in CRC cell lines, in tissue microarrays (TMAs) and in public datasets. Overexpression of APC11 mRNA was associated with chromosomal instability, lymphovascular invasion and residual tumor. Regression models accounting for the effects of well-known protein markers highlighted association of APC11 protein expression with residual tumor (odds ratio: OR = 6.51; 95% confidence intervals: CI = 1.54-27.59; P = 0.012) and metastasis at diagnosis (OR = 3.87; 95% CI = 1.20-2.45; P = 0.024). Overexpression of APC11 protein was also associated with worse distant relapse-free survival (hazard ratio: HR = 2.60; 95% CI = 1.26-5.37; P = 0.01) and worse overall survival (HR = 2.69; 95% CI = 1.31-5.51; P = 0.007). APC11 overexpression in primary CRC thus represents a potentially novel theranostic marker of metastatic CRC.

USP9X Limits Mitotic Checkpoint Complex Turnover to Strengthen the Spindle Assembly Checkpoint and Guard against Chromosomal Instability.

Faithful chromosome segregation during mitosis depends on the spindle assembly checkpoint (SAC), which delays progression through mitosis until every chromosome has stably attached to spindle microtubules via the kinetochore. We show here that the deubiquitinase USP9X strengthens the SAC by antagonizing the turnover of the mitotic checkpoint complex produced at unattached kinetochores. USP9X thereby opposes activation of anaphase-promoting complex/cyclosome (APC/C) and specifically inhibits the mitotic degradation of SAC-controlled APC/C substrates. We demonstrate that depletion or loss of USP9X reduces the effectiveness of the SAC, elevates chromosome segregation defects, and enhances chromosomal instability (CIN). These findings provide a rationale to explain why loss of USP9X could be either pro- or anti-tumorigenic depending on the existing level of CIN.

A single-nucleotide exon found in Arabidopsis.

The presence of introns in gene-coding regions is one of the most mysterious evolutionary inventions in eukaryotic organisms. It has been proposed that, although sequences involved in intron recognition and splicing are mainly located in introns, exonic sequences also contribute to intron splicing. The smallest constitutively spliced exon known so far has 6 nucleotides, and the smallest alternatively spliced exon has 3 nucleotides. Here we report that the Anaphase Promoting Complex subunit 11 (APC11) gene in Arabidopsis thaliana carries a constitutive single-nucleotide exon. In vivo transcription and translation assays performed using APC11-Green Fluorescence Protein (GFP) fusion constructs revealed that intron splicing surrounding the single-nucleotide exon is effective in both Arabidopsis and rice. This discovery warrants attention to genome annotations in the future.