Potential regulatory mechanism and clinical significance of synaptotagmin binding cytoplasmic RNA interacting protein in colorectal cancer

BACKGROUND Colorectal cancer(CRC)causes many deaths worldwide.Synaptotagmin binding cytoplasmic RNA interacting protein(SYNCRIP)is an RNA-binding protein that plays an important role in multiple cancers by epigenetically targeting some genes.Our study will examine the expression,potential effect,biological function and clinical value of SYNCRIP in CRC.AIM To examine the expression,potential effect,biological function and clinical value METHODS The expression of SYNCRIP was examined by immunohistochemistry arrays and high-throughput data.The effect of SYNCRIP gene in CRC cell growth was evaluated by CRISPR-Cas9 technology.The target genes of SYNCRIP were calculated using various algorithms,and the molecular mechanism of SYNCRIP in CRC was explored by mutation analysis and pathway analysis.The clinical value of SYNCRIP in prognosis and radiotherapy was revealed via evidence-based medicine methods.RESULTS The protein and mRNA levels of SYNCRIP were both highly expressed in CRC samples compared to nontumorous tissue based on 330 immunohistochemistry arrays and 3640 CRC samples.Cells grew more slowly in eleven CRC cell lines after knocking out the SYNCRIP gene.SYNCRIP could epigenetically target genes to promote the occurrence and development of CRC by boosting the cell cycle and affecting the tumor microenvironment.In addition,CRC patients with high SYNCRIP expression are more sensitive to radiotherapy.CONCLUSION SYNCRIP is upregulated in CRC,and highly expressed SYNCRIP can accelerate CRC cell division by exerting its epigenetic regulatory effects.In addition,SYNCRIP is expected to become a potential biomarker to predict the effect of radiotherapy.

VALUATION DE L'EXPRESSION DES RGULATEURS DU CYCLE CELLULAIRE EN G1/S DANS LE CARCINOME PIDERMO DE DE L'CSOPHAGE

Objective To study the expression of p16, cyclin D1, Rb and phosphorylated Rb(Ser795) in the esophageal squamous cell carcinoma. Methods Immunohistochemistry was performed and analysed on 34 cases of paraffin-embedded tissues. Results The expression of phosphorylated Rb(Ser795) was positively correlated to that of cyclin D1 (r= 0.401, P= 0.021) and inversely to that of p16 (r= -0.348, P= 0.044). In stepwise regression and the best subset regression, the expression of p16 (P=0.034) and phosphorylated Rb(Ser795) (P= 0.030) were the only determinants of the mitotic index. Conclusion The expression of phosphorylated Rb(Ser795) could be considered as a mark of the interaction between p16 and cyclin D1. The detection of phosphorylated Rb, p16 and cyclin D1 will be possibly helpful to the oncogenesis investigation on the esophageal carcinoma.

Regulators of alternative polyadenylation operate at the transition from mitosis to meiosis

In the sexually reproductive organisms, gametes are produced by meiosis following a limited mitotic amplification. However, the intrinsic program switching cells from mitotic to meiotic cycle is unclear.Alternative polyadenylation（APA） is a highly conserved means of gene regulation and is achieved by the RNA 30-processing machinery to generate diverse 30 UTR profiles. In Drosophila spermatogenesis, we observed distinct profiles of transcriptome-wide 30 UTR between mitotic and meiotic cells. In mutant germ cells stuck in mitosis, 30 UTRs of hundreds of genes were consistently shifted. Remarkably, altering the levels of multiple 30-processing factors disrupted germline＇s progression to meiosis, indicative of APA＇s active role in this transition. An RNA-binding protein（RBP） Tut could directly bind 30 UTRs of 30-processing factors whose expressions were repressed in the presence of Tut-containing complex. Further,we demonstrated that this RBP complex could execute the repression post-transcriptionally by recruiting CCR4/Twin of deadenylation complex. Thus, we propose that an RBP complex regulates the dynamic APA profile to promote the mitosis-to-meiosis transition.

Investigation of nuclear enzyme topoisomerase as a putative molecular target of monohaloacetonitrile disinfection by-products

Disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. Yet the molecular mechanisms of their toxicity are not well understood. To investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase Ⅱ in Chinese hamster ovary cells was examined. We showed a concentration-dependent inhibition of DNA decatenation activity of topoisomerase under acellular conditions while in vitro monohaloacetonitrile treatment expressed mixed results. The working hypothesis, that topoisomerase Ⅱ is a molecular target of monohaloacetonitriles, was only partially supported.Nevertheless, this research serves as a starting point toward molecular mechanisms of toxic action of monohaloacetonitriles.