Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.

Our study demonstrates that the CIC-ETV4-MMP1 axis is a regulatory module controlling HCC progression. (Hepatology 2018;67:2287-2301).

Summary Plants have recently received a great deal of attention as a means of producing recombinant proteins. Despite this, a limited number of recombinant proteins are currently on the market and, if plants are to be more widely used, a cost‐effective and efficient purification method is urgently needed. Although affinity tags are convenient tools for protein purification, the presence of a tag on the recombinant protein is undesirable for many applications. A cost‐effective method of purification using an affinity tag and the removal of the tag after purification has been developed. The family 3 cellulose‐binding domain ( CBM 3), which binds to microcrystalline cellulose, served as the affinity tag and the small ubiquitin‐related modifier ( SUMO ) and SUMO ‐specific protease were used to remove it. This method, together with size‐exclusion chromatography, enabled purification of human interleukin‐6 ( hIL 6) with a yield of 18.49 mg/kg fresh weight from leaf extracts of Nicotiana benthamiana following Agrobacterium ‐mediated transient expression. Plant‐produced hIL 6 (P‐ hIL 6) contained less than 0.2 EU/μg (0.02 ng/mL) endotoxin. P‐ hIL 6 activated the Janus kinase‐signal transducer and activator of transcriptional pathways in human LNC aP cells, and induced expression of IL ‐21 in activated mouse CD 4 + T cells. This approach is thus a powerful method for producing recombinant proteins in plants.

Background: Although major driver gene mutations have been identified, the complex molecular heterogeneity of colorectal cancer (CRC) remains unclear. Capicua (CIC) functions as a tumor suppressor in various types of cancers; however, its role in CRC progression has not been examined. Methods: Databases for gene expression profile in CRC patient samples were used to evaluate the association of the levels of CIC and Polyoma enhancer activator 3 (PEA3) group genes (ETS translocation variant 1 (ETV1), ETV4, and ETV5), the best-characterized CIC targets in terms of CIC functions, with clinicopathological features of CRC. CIC and ETV4 protein levels were also examined in CRC patient tissue samples. Gain-and loss-of function experiments in cell lines and mouse xenograft models were performed to investigate regulatory functions of CIC and ETV4 in CRC cell growth and invasion. qRT-PCR and western blot analyses were performed to verify the CIC regulation of ETV4 expression in CRC cells. Rescue experiments were conducted using siRNA against ETV4 and CIC-deficient CRC cell lines. Results: CIC expression was decreased in the tissue samples of CRC patients. Cell invasion, migration, and proliferation were enhanced in CIC-deficient CRC cells and suppressed in CIC-overexpressing cells. Among PEA3 group genes, ETV4 levels were most dramatically upregulated and inversely correlated with the CIC levels in CRC patient samples. Furthermore, derepression of ETV4 was more prominent in CIC-deficient CRC cells, when compared with that observed for ETV1 and ETV5. The enhanced cell proliferative and invasive capabilities in CIC-deficient CRC cells were completely recovered by knockdown of ETV4. Conclusion: Collectively, the CIC-ETV4 axis is not only a key module that controls CRC progression but also a novel therapeutic and/or diagnostic target for CRC.