High expression of serine and arginine-rich splicing factor 9 (SRSF9) is associated with hepatocellular carcinoma progression and a poor prognosis.

Background: Serine and arginine-rich splicing factor 9 (SRSF9) has been linked to the occurrence and progression of various cancers; however, its effects and mechanism of action hepatocellular carcinoma (HCC) have not been reported. In this study, we used a bioinformatics approach and in vitro assays to evaluate the expression of SRSF9 in HCC, its prognostic value, and its underlying regulatory mechanisms, including analyses of related pathways and the role of methylation.

Methods: Transcriptomic and DNA methylation data for 357 HCC cases and 50 paratumor tissues in The Cancer Genome Atlas database were obtained.

Increased Predicts Poor Prognosis in Patients With Colorectal Carcinoma.

Colorectal cancer is one of the most common malignant tumors in the digestive system. Traditional diagnosis and treatment methods have not significantly improved the overall survival of patients. In this study, we explored the value of as a biomarker in predicting the prognosis of colorectal cancer patients.

Functional TCR T cell screening using single-cell droplet microfluidics.

Adoptive T cell transfer, in particular TCR T cell therapy, holds great promise for cancer immunotherapy with encouraging clinical results. However, finding the right TCR T cell clone is a tedious, time-consuming, and costly process. Thus, there is a critical need for single cell technologies to conduct fast and multiplexed functional analyses followed by recovery of the clone of interest.

Protective Effect of Hericium erinaceus on Alcohol Induced Hepatotoxicity in Mice.

We investigated the effects of Hericium erinaceus (HEM) on liver injury induced by acute alcohol administration in mice. Mice received ethanol (5 g/kg BW) by gavage every 12 hrs for a total of 3 doses. HEM (200 mg/kg BW) was gavage before ethanol administration.

A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia.

RAD51 recombinase activity plays a critical role for cancer cell proliferation and survival, and often contributes to drug-resistance. Abnormally elevated RAD51 function and hyperactive homologous recombination (HR) rates have been found in a panel of cancers, including breast cancer and chronic myeloid leukaemia (CML). Directly targeting RAD51 and attenuating the deregulated RAD51 activity has therefore been proposed as an alternative and supplementary strategy for cancer treatment.

Phosphorylation of the Ndc80 complex protein, HEC1, by Nek2 kinase modulates chromosome alignment and signaling of the spindle assembly checkpoint.

The spindle assemble checkpoint (SAC) is critical for accurate chromosome segregation. Hec1 contributes to chromosome segregation in part by mediating SAC signaling and chromosome alignment. However, the molecular mechanism by which Hec1 modulates checkpoint signaling and alignment remains poorly understood.

Aurora-A phosphorylates Augmin complex component Hice1 protein at an N-terminal serine/threonine cluster to modulate its microtubule binding activity during spindle assembly.

Proper assembly of mitotic spindles requires Hice1, a spindle-associated protein. Hice1 possesses direct microtubule binding activity at its N-terminal region and contributes to intraspindle microtubule nucleation as a subunit of the Augmin complex. However, whether microtubule binding activity of Hice1 is modulated by mitotic regulators remains unexplored.

14-3-3 adaptor proteins recruit AID to 5'-AGCT-3'-rich switch regions for class switch recombination.

Class switch DNA recombination (CSR) is the mechanism that diversifies the biological effector functions of antibodies. Activation-induced cytidine deaminase (AID), a key protein in CSR, targets immunoglobulin H (IgH) switch regions, which contain 5'-AGCT-3' repeats in their core. How AID is recruited to switch regions remains unclear.

Hec1 contributes to mitotic centrosomal microtubule growth for proper spindle assembly through interaction with Hice1.

Previous studies have stipulated Hec1 as a conserved kinetochore component critical for mitotic control in part by directly binding to kinetochore fibers of the mitotic spindle and by recruiting spindle assembly checkpoint proteins Mad1 and Mad2. Hec1 has also been reported to localize to centrosomes, but its function there has yet to be elucidated. Here, we show that Hec1 specifically colocalizes with Hice1, a previously characterized centrosomal microtubule-binding protein, at the spindle pole region during mitosis.

Synthesis and biological evaluation of a series of novel inhibitor of Nek2/Hec1 analogues.

High expression in cancer 1 (Hec1) is an oncogene overly expressed in many human cancers. Small molecule inhibitor of Nek2/Hec1 (INH) targeting the Hec1 and its regulator, Nek2, in the mitotic pathway, was identified to inactivate Hec1/Nek2 function mediated by protein degradation that subsequently leads to chromosome mis-segregation and cell death. To further improve the efficacy of INH, a series of INH analogues were designed, synthesized, and evaluated.

Stereoselective synthesis of chiral IBR2 analogues.

Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1:1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared.

Small molecule targeting the Hec1/Nek2 mitotic pathway suppresses tumor cell growth in culture and in animal.

Hec1 is a conserved mitotic regulator critical for spindle checkpoint control, kinetochore functionality, and cell survival. Overexpression of Hec1 has been detected in a variety of human cancers and is linked to poor prognosis of primary breast cancers. Through a chemical genetic screening, we have identified a small molecule, N-(4-[2,4-dimethyl-phenyl]-thiazol-2-yl)-benzamide (INH1), which specifically disrupts the Hec1/Nek2 interaction via direct Hec1 binding.

Role of SUV3 helicase in maintaining mitochondrial homeostasis in human cells.

In yeast mitochondria, RNA degradation takes place through the coordinated activities of ySuv3 helicase and yDss1 exoribonuclease (mtEXO), whereas in bacteria, RNA is degraded via RNaseE, RhlB, PNPase, and enolase. Yeast lacking the Suv3 component of the mtEXO form petits and undergo a toxic accumulation of omega intron RNAs. Mammalian mitochondria resemble their prokaryotic origins by harboring a polyadenylation-dependent RNA degradation mechanism, but whether SUV3 participates in regulating RNA turnover in mammalian mitochondria is unclear.

A novel role of the chromokinesin Kif4A in DNA damage response.

Chromokinesins are microtubule-motor molecules that possess chromatin binding activity and are important for mitotic and meiotic regulation. The chromokinesin-member Kif4A is unique in that it localizes to nucleus during interphase of the cell cycle. Kif4 deletion by gene targeting in mouse embryonic cells was known to associate with DNA damage response.

Structural requirements of chromokinesin Kif4A for its proper function in mitosis.

Human Kif4A is a member of the Kinesin-4 family of kinesins. Kif4A is thought to be a bona fide chromokinesin because it possesses a motor domain and associates with condensed chromosomes during mitosis. Genetic deletion of Kif4A promotes tumorigenic phenotypes in mouse embryonic cells.

Hice1, a novel microtubule-associated protein required for maintenance of spindle integrity and chromosomal stability in human cells.

Spindle integrity is critical for efficient mitotic progression and accurate chromosome segregation. Deregulation of spindles often leads to structural and functional aberrations, ultimately promoting segregation errors and aneuploidy, a hallmark of most human cancers. Here we report the characterization of a previously identified human sarcoma antigen (gene located at 19p13.

RINT-1 serves as a tumor suppressor and maintains Golgi dynamics and centrosome integrity for cell survival.

Faithful mitotic partitioning of the Golgi apparatus and the centrosome is critical for proper cell division. Although these two cytoplasmic organelles are probably coordinated during cell division, supporting evidence of this coordination is still largely lacking. Here, we show that the RAD50-interacting protein, RINT-1, is localized at the Golgi apparatus and the centrosome in addition to the endoplasmic reticulum.

CtIP, a multivalent adaptor connecting transcriptional regulation, checkpoint control and tumor suppression.

CtIP was originally characterized as an interacting protein for the transcriptional corepressor CtBP. In addition to transcriptional regulation, CtIP plays an important role in the DNA damage response and cell cycle checkpoint control. Recent evidence points to a viral factor-like S phase promoting activity of CtIP in counteracting Rb repression to facilitate E2F-directed transactivation during the G(1)/S transition.

Assembly of functional ALT-associated promyelocytic leukemia bodies requires Nijmegen Breakage Syndrome 1.

Immortalized cells maintain telomere length through either a telomerase-dependent process or a telomerase-independent pathway termed alternative lengthening of telomeres (ALT). Homologous recombination is implicated in the ALT pathway in both yeast and human ALT cells. In ALT cells, two types of DNA double-strand break repair and homologous recombination factors, the Rad50/Mre11/NBS1 complex and Rad51/Rad52 along with replication factors (RPA) and telomere binding proteins (TRF1 and TRF2), are associated with the ALT-associated PML body (APB).