Retraction Notice to: m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylating PJA2 and inhibiting Wnt signaling.

[This retracts the article DOI: 10.1016/j.omtn.2021.06.005.].

Double-Interpenetrating-Network Lignin-based Epoxy Resin Adhesives for Resistance to Extreme Environment.

The gradually depleting fossil resources and the biosafety of bisphenol A have always restricted the green development of the traditional epoxy resin field. In this Article, biomass macromolecule lignin sulfonates are selected as the raw material instead of traditional bisphenol A to prepare lignin-based epoxy resin adhesives. Lignin sulfonates are chemically modified and combined with a cross-linking agent to form lignin-based epoxy resin adhesives with double-interpenetrating-network structures. The resulting lignin-based epoxy adhesive exhibits a maximum tensile shear strength of 11.29 MPa, which is 213% higher than the strength before chemical modification. The tensile shear strength of the adhesive is still 10.13 MPa after 12 h of immersion in water (20 °C), and its tensile shear strength is 9.30 MPa after 12 h of immersion in boiling water (100 °C). The high-temperature and high-humidity environment has no significant effect on the properties of the resulting lignin-based epoxy adhesive.

m6A demethylase FTO suppresses pancreatic cancer tumorigenesis by demethylating PJA2 and inhibiting Wnt signaling.

Pancreatic cancer is the deadliest malignancy of the digestive system and is the seventh most common cause of cancer-related deaths worldwide. The incidence and mortality of pancreatic cancer continue to increase, and its 5-year survival rate remains the lowest among all cancers. N6-methyladenine (m6A) is the most abundant reversible RNA modification in various eukaryotic messenger and long noncoding RNAs and plays crucial roles in the occurrence and development of cancers. However, the role of m6A in pancreatic cancer remains unclear. The present study aimed to explore the role of m6A and its regulators in pancreatic cancer and assess its underlying molecular mechanism associated with pancreatic cancer cell proliferation, invasion, and metastasis. Reduced expression of the m6A demethylase, fat mass and obesity-associated protein (FTO), was responsible for the high levels of m6A RNA modification in pancreatic cancer. Moreover, FTO demethylated the m6A modification of praja ring finger ubiquitin ligase 2 (PJA2), thereby reducing its mRNA decay, suppressing Wnt signaling, and ultimately restraining the proliferation, invasion, and metastasis of pancreatic cancer cells. Altogether, this study describes new, potential molecular therapeutic targets for pancreatic cancer that could pave the way to improve patient outcome.

Discovery of novel nitrogenous heterocyclic-containing quinoxaline-1,4-di-N-oxides as potent activator of autophagy in M.tb-infected macrophages.

As a continuation of our research on antimycobacterial agents, a series of novel quinoxaline-1,4-di-N-oxides (QdNOs) containing various nitrogenous heterocyclic moieties at the R6 position were designed and synthesized. Antimycobacterial activities, as well as the cytotoxic effects, of the compounds were assayed. Four compounds (6b, 6f, 6n, and 6o), characterized by 2-carboxylate ethyl or benzyl ester, 6-imidazolyl or 1,2,4-triazolyl, and a 7-fluorine group, exhibited the most potent antimycobacterial activity against M.tb strain H37Rv (MIC ≤ 0.25 µg/mL) with low toxicity in VERO cells (SI = 169.3-412.1). Compound 6o also exhibited excellent antimycobacterial activity in an M.tb-infected macrophage model and was selected for further exploration of the mode of antimycobacterial action of QdNOs. The results showed that compound 6o was capable of disrupting membrane integrity and disturbing energy homeostasis in M.tb. Furthermore, compound 6o noticeably increased cellular ROS levels and, subsequently, induced autophagy in M.tb-infected macrophages, possibly indicating the pathways of QdNOs-mediated inhibition of intracellular M.tb replication. The in vivo pharmacokinetic (PK) profiles indicated that compounds 6o was acceptably safe and possesses favorable PK properties. Altogether, these findings suggest that compound 6o is a promising antimycobacterial candidate for further research.

Genetic alterations and functional networks of m6A RNA methylation regulators in pancreatic cancer based on data mining.

BACKGROUND: Pancreatic cancer is a fatal malignancy of the digestive system and the 5-year survival rate remains low. Therefore, new molecular therapeutic targets are required to improve treatments, prognosis, and the survival of patients. N6-methyladenosine (m6A) is the most prevalent reversible methylation in mammalian messenger RNA (mRNA) and has critical roles in the tumorigenesis and metastasis of various malignancies. However, the role of m6A in pancreatic cancer is still unclear. Exploring genetic alterations and functional networks of m6A regulators in pancreatic cancer may provide new strategies for its treatment. METHODS: In this study, we used data from the Cancer Genome Atlas (TCGA) database and other public databases through cBioPortal, LinkedOmics, UALCAN, GEPIA, STRING, and the database for annotation, visualization, and integrated discovery (DAVID) to systematically analyze the molecular alterations and functions of 20 main m6A regulators in pancreatic cancer. RESULTS: We found that m6A regulators had widespread genetic alterations, and that their expression levels were significantly correlated with pancreatic cancer malignancy. Moreover, m6A regulators were associated with the prognosis of pancreatic cancer patients. CONCLUSIONS: m6A regulators play a crucial part in the occurrence and development of pancreatic cancer. Our study will guide further studies of m6A RNA modification in pancreatic cancer and could potentially provide new strategies for pancreatic cancer treatment.

Tissue Depletion of Olaquindox and Its Six Metabolites in Pigs and Broilers: Identification of a Suitable Marker Residue.

The depletion profiles of olaquindox and its six major metabolites, including O1 (N 1-deoxyolaquindox), O2 (deoxyolaquindox), O3 (2-carboxamide-3-methylquinoxaline-N 4-oxide), O4 (2-carboxymethylaminocarbonyl-3-methylquinoxaline-N 4-oxide), O5 (2-carboxymethylaminocarbonyl-3-methylquinoxaline), and O6 [3-methyl-quinoxaline-2-carboxylic acid (MQCA)] were studied with a sensitive and accurate HPLC-UV method in pigs and broilers after oral administration of olaquindox at the rate of 50 mg kg-1 feed for 14 consecutive days. Five medicated pigs and six medicated broilers and one control animal for each time point were anesthetized and killed at different time points (6 h and 1, 3, 7, and 14 days for pigs and 6 h and 1, 3, 5, and 7 days for broilers) after ingestion of the medicated feed ceased and samples of muscle, liver, kidney, and fat were collected. The samples were assayed using a liquid chromatographic method. Mean concentrations of O2 (deoxyolaquindox) metabolite residues in all tissues of pigs were higher than other metabolite residues at each time point. MQCA was detected at lower concentrations and eliminated more rapidly than deoxyolaquindox (calculated t 1/2 1.78-2.28 days vs. t 1/2 2.04-2.46 days). The elimination half-lives of deoxyolaquindox residue in broilers' liver and kidney tissues (t 1/2 >4 days) were much longer than those in pigs. Thus, the use of olaquindox in poultry is clearly inappropriate, as significant drug residues will occur without a withdrawal time. The results that deoxyolaquindox occurs at higher concentrations in kidney tissue and is more persistent than other residues in edible tissues of pigs which indicate that deoxyolaquindox is the most relevant marker residue and should be monitored in the routine surveillance of olaquindox-related residues in foods of animal origin.

Fabrication of tunable, high-molecular-weight polymeric nanoparticles via ultrafast acoustofluidic micromixing.

High-molecular-weight polymeric nanoparticles are critical to increasing the loading efficacy and tuning the release profile of targeted molecules for medical diagnosis, imaging, and therapeutics. Although a number of microfluidic approaches have attained reproducible nanoparticle synthesis, it is still challenging to fabricate nanoparticles from high-molecular-weight polymers in a size and structure-controlled manner. In this work, an acoustofluidic platform is developed to synthesize size-tunable, high-molecular-weight (>45 kDa) poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) nanoparticles without polymer aggregation by exploiting the characteristics of complete and ultrafast mixing. Moreover, the acoustofluidic approach achieves two features that have not been achieved by existing microfluidic approaches: (1) multi-step (≥2) sequential nanoprecipitation in a single device, and (2) synthesis of core-shell structured PLGA-PEG/lipid nanoparticles with high molecular weights. The developed platform expands microfluidic potential in nanomaterial synthesis, where high-molecular-weight polymers, multiple reagents, or sequential nanoprecipitations are needed.

ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition.

Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a potential target for improving radiosensitivity. Materials and Methods: The radiosensitivity of NSCLC cells was evaluated by flow cytometry, colony formation assays, immunofluorescence, and Western blotting. Bioinformatics assay was used to identify the effect of ITGB1 and YAP1 expression in NSCLC tissues. Results: ITGB1 mRNA and protein expression levels were higher in H460R than in the parental H460 cells. We observed lower clonogenic survival and cell viability and a higher rate of apoptosis of ITGB1-knockdown A549 and H460R cells than of wild type cells post-irradiation. Transfection with an ITGB1 short hairpin (sh) RNA enhanced radiation-induced DNA damage and G2/M phase arrest. Moreover, ITGB1 induced epithelial-mesenchymal transition (EMT) of NSCLC cells. Silencing ITGB1 suppressed the expression and intracellular translocation of Yes-associated protein 1 (YAP1), a downstream effector of ITGB1. Conclusions: ITGB1 may induce radioresistance via affecting DNA repair and YAP1-induced EMT. Taken together, our data suggest that ITGB1 is an attractive therapeutic target to overcome NSCLC cell radioresistance.

Novel lignin-containing high-performance adhesive for extreme environment.

The gradual depletion of petroleum is a main challenge restricting the development for the fine chemicals, such as epoxy resin adhesive. In this study, a novel lignin-containing high-performance epoxy resin adhesive is synthesized using lignin as precursor material. Lignin is a unique biomacromolecule with three dimensional network structure, large molecular weight, and aromatic structure. The lignin is simply hydrolyzed and modified by epichlorohydrin to obtain lignin-based epoxy prepolymer. The hydrolysis process effectively reduces the molecular weight and improves the chemical reactivity of lignin, thus increasing the number of modified functional groups and the dispersibility of lignin concurrently. With the introduction of the lignin-based epoxy prepolymers, the shear strength of the adhesive increases obviously and reaches 10.42 MPa, which displays 228% of the shear strength of commercial epoxy resin adhesives. Furthermore, the lignin-containing epoxy resin adhesive still displays excellent mechanical properties in extreme environments, including extreme temperature and high humidity environment.

Design, Synthesis, and Biological Evaluation of Novel Thiazolidinone-Containing Quinoxaline-1,4-di-N-oxides as Antimycobacterial and Antifungal Agents.

Tuberculosis and fungal infections can pose serious threats to human health. In order to find novel antimicrobial agents, 26 novel quinoxaline-1,4-di-N-oxides containing a thiazolidinone moiety were designed and synthesized, and their antimycobacterial activities were evaluated. Among them, compounds 2t, 2u, 2y, and 2z displayed the most potent antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (minimal inhibitory concentration [MIC] = 1.56 µg/mL). The antifungal activity of all the compounds was also evaluated against Candida albicans, Candida tropicalis, Aspergillus fumigatus, and Cryptococcus neoformans. Compounds 2t, 2u, 2y, and 2z exhibited potential antifungal activities, with an MIC between 2 and 4 µg/mL. Comparative molecular field analysis (CoMFA: q 2 = 0.914, r 2 = 0.967) and comparative molecular similarity index analysis (CoMSIA: q 2 = 0.918, r 2 = 0.968) models were established to investigate the structure and antimycobacterial activity relationship. The results of contour maps revealed that electronegative and sterically bulky substituents play an important role in the antimycobacterial activity. Electronegative and sterically bulky substituents are preferred at the C7 position of the quinoxaline ring and the C4 position of the phenyl group to increase the antimycobacterial activity. Additionally, more hydrogen bond donor substituents should be considered at the C2 side chain of the quinoxaline ring to improve the activity.

A disposable acoustofluidic chip for nano/microparticle separation using unidirectional acoustic transducers.

Separation of nano/microparticles based on surface acoustic waves (SAWs) has shown great promise for biological, chemical, and medical applications ranging from sample purification to cancer diagnosis. However, the permanent bonding of a microchannel onto relatively expensive piezoelectric substrates and excitation transducers renders the SAW separation devices non-disposable. This limitation not only requires cumbersome cleaning and increased labor and material costs, but also leads to cross-contamination, preventing their implementation in many biological, chemical, and medical applications. Here, we demonstrate a high-performance, disposable acoustofluidic platform for nano/microparticle separation. Leveraging unidirectional interdigital transducers (IDTs), a hybrid channel design with hard/soft materials, and tilted-angle standing SAWs (taSSAWs), our disposable acoustofluidic devices achieve acoustic radiation forces comparable to those generated by existing permanently bonded, non-disposable devices. Our disposable devices can separate not only microparticles but also nanoparticles. Moreover, they can differentiate bacteria from human red blood cells (RBCs) with a purity of up to 96%. Altogether, we developed a unidirectional IDT-based, disposable acoustofluidic platform for micro/nanoparticle separation that can achieve high separation efficiency, versatility, and biocompatibility.

Transcription levels and prognostic significance of the NFI family members in human cancers.

BACKGROUND: The nuclear factor I (NFI) is a family of transcription factors consisting of four distinct but closely related genes, NFIA, NFIB, NFIC and NFIX, which are important in the development of various tissues and organs in mammals. Recent study results have shown that NFI family may play a critical role in the progression of various human tumors and have been identified as key tumor suppressors and oncogenes for many cancers. However, the expression levels and distinctive prognostic values of the NFI family remain poorly explored in most cancers. MATERIALS AND METHODS: In the present study, the differences in mRNA expression of the NFI family in various cancers were investigated using the Oncomine and TCGA databases, and the mRNA expression, genetic alteration and DNA methylation of the NFI family members in various cancers were examined using cBioPortal for Cancer Genomics. In addition, the prognostic significance of the NFI family was assessed in multiple cancers using the Kaplan-Meier plotter (KM plotter) and SurvExpress databases. RESULTS: The mRNA expression levels in the NFI family were significantly downregulated in most cancers compared with normal tissues and DNA hypermethylation might downregulate the NFI family expression. Although NFIX expression was not downregulated in kidney, colorectal and prostate cancers. Furthermore, NFIB expression was upregulated in gastric cancer. Further survival analyses based on the KM plotter and SurvExpress databases showed dysregulations of the NFI genes were significantly correlated with survival outcomes in breast, lung, and head and neck cancers. Decreased expression levels of NFIA, NFIB and NFIC were associated with poor overall survival (OS) in head and neck cancer. Low mRNA expression of NFIA and NFIB was significantly associated with OS and first progression in lung adenocarcinoma, but not in lung squamous cell carcinoma. In addition, potential correlations between NFI family members and survival outcomes were also observed in liver, esophageal, kidney and cervical cancer. CONCLUSION: The results from the present study indicated certain members of the NFI family could be promising therapeutic targets and novel prognostic biomarkers for human cancers.

Multiple metachronous rare primary malignant tumors: A case report.

Multiple primary malignant tumors (MPMTs) are rarely seen among the patients with malignant neoplasms. Moreover, the existence of five MPMTs in the same patient is an extremely rare phenomenon. In this case, a 42-year-old male patient developed five metachronous MPMTs within 16 years and the duration between each malignant tumor shortened with the progression of the disease. Multidisciplinary treatments were used on this patient and he fought against the cancers until the end of his life. Our report provides us with a new awareness of MPMTs, which should be considered when we come across with cancer patients who develop various unexplainable symptoms after the diagnosis of the first neoplasm.

ceRNA network analysis reveals prognostic markers for glioblastoma.

Glioblastoma (GBM) is a common aggressive cancer that originates in the brain, which has a poor prognosis. It is therefore crucial to understand its underlying genetic mechanisms in order to develop novel therapies. The present study aimed to identify some prognostic markers and candidate therapeutic targets for GBM. To do so, RNA expression levels in tumor and normal tissues were compared by microarray analysis. The differential expression of RNAs in normal and cancer tissues was analyzed, and a competing endogenous RNA (ceRNA) network was constructed for pathway analysis. The results revealed that RNA expression patterns were considerably different between normal and tumor samples. A ceRNA network was therefore constructed with the differentially expressed RNAs. ETS variant 5 (ETV5), myocyte enhancer factor 2C and ETS transcription factor (ELK4) were considerably enriched in the significant pathway of 'transcriptional misregulation in cancer'. In addition, prognostic analysis demonstrated that ETV5 and ELK4 expression levels were associated with the survival time of patients with GBM. These results suggested that ELK4 and ETV5 may be prognostic markers for GBM, and that their microRNAs may be candidate therapeutic targets.

A novel role for NFIA in restoring radiosensitivity in radioresistant NSCLC cells by downregulating the AKT and ERK pathways.

Radioresistance remains the most challenging issue leading to radiotherapy failure in the treatment of non-small cell lung cancer (NSCLC). The nuclear factor IA (NFIA) is associated with tumor response to treatments in many cancers, but its role in NSCLC radioresistance remains unclear. Here, we established two radioresistant NSCLC cell lines, H226R and H460R, by dose-gradient irradiation to investigate the function of NFIA in NSCLC radioresistance. The results showed a dramatically reduced expression of NFIA in radioresistant cells accompanied with elevated phosphorylation of AKT and ERK, when compared with their parental cells. Overexpression of NFIA restored the sensitivity of radioresistant cells to radiation through increased ionizing radiation (IR)-induced apoptosis and DNA damage by downregulating p-AKT and p-ERK, whereas knockdown of NFIA promoted radioresistance of the parental cells. Our findings suggested that NFIA enhanced cell radiosensitivity by downregulating p-AKT and p-ERK in NSCLC. Our study fills a gap in the field of NFIA and radioresistance, and establishes a mechanistic foundation to improve radiotherapy efficiency in NSCLC patients.

The nature and epidemiology of OqxAB, a multidrug efflux pump.

Background: OqxAB efflux pump has been found to mediate multidrug resistance (MDR) in various bacteria over the past decades. The updates on the nature and epidemiology of OqxAB efflux pump need to be fully reviewed to broaden our understanding of this MDR determinant. Methods: A literature search using the keyword of "oqxAB" was conducted in the online databases of Pubmed and ISI Web of Science with no restriction on the date of publication. The 87 publications were included into this review as references due to their close relevance to the nature and/or epidemiology of OqxAB efflux pump. Results: The oqxAB gene generally locates on chromosome and/or plasmids flanked by IS26-like elements in clinical isolates of Enterobacteriaceae and Klebsiella pneumoniae, conferring low to intermediated resistance to quinoxalines, quinolones tigecycline, nitrofurantoin, several detergents and disinfectants (benzalkonium chloride, triclosan and SDS). It could co-spread with other antimicrobial resistance genes (blaCTX-M, rmtB and aac(6')-Ib etc.), virulence genes and heavy metal resistance genes (pco and sil operons). Both RarA (activator) and OqxR (repressor) play important roles on regulation of the expression of OqxAB. Conclusions: The dissemination of oqxAB gene may pose a great risk on food safety and public health. Further investigation and understanding of the natural functions, horizontal transfer, and regulation mechanism of the OqxAB efflux pump will aid in future strategies of antimicrobial usage.

Resistance and Virulence Mechanisms of Escherichia coli Selected by Enrofloxacin in Chicken.

This study aimed to investigate the genetic characteristics, antibiotic resistance patterns, and novel mechanisms involved in fluoroquinolone (FQ) resistance in commensal Escherichia coli isolates. The E. coli isolates were recovered from a previous clinical study and subjected to antimicrobial susceptibility testing and molecular typing. Known mechanisms of FQ resistance (target site mutations, plasmid-mediated quinolone resistance [PMQR] genes, relative expression levels of efflux pumps and porins) were detected using DNA sequencing of PCR products and real-time quantitative PCR. Whole-genome shotgun sequencing was performed on 11 representative strains to screen for single nucleotide polymorphisms (SNPs). The function of a key SNP (A1541G) was investigated by site-directed mutagenesis and allelic exchange. The results showed that long-term enrofloxacin treatment selected multidrug-resistant (MDR) E. coli isolates in the chicken gut and that these E. coli isolates had diverse genetic backgrounds. Multiple genetic alterations, including double mutations on GyrA (S83L and D87N), a single mutation on ParC (S80I) and ParE (S458E), activation of efflux pumps, and the presence of the QnrS1 protein, contributed to the high-level FQ resistance (enrofloxacin MIC [MICENR] ≥ 128 µg/ml), while the relatively low-level FQ resistance (MICENR = 8 or 16 µg/ml) was commonly mediated by decreased expression of the porin OmpF, besides enhancement of the efflux pumps. No significant relationship was observed between resistance mechanisms and virulence genes. Introduction of the A1541G mutation on aegA was able to increase FQ susceptibility by 2-fold. This study contributes to a better understanding of the development of MDR and the differences underlying the mechanisms of high-level and low-level FQ resistance in E. coli.

Subgroup analysis reveals molecular heterogeneity and provides potential precise treatment for pancreatic cancers.

BACKGROUND: The relationship between molecular heterogeneity and clinical features of pancreatic cancer remains unclear. In this study, pancreatic cancer was divided into different subgroups to explore its specific molecular characteristics and potential therapeutic targets. PATIENTS AND METHODS: Expression profiling data were downloaded from The Cancer Genome Atlas database and standardized. Bioinformatics techniques such as unsupervised hierarchical clustering was used to explore the optimal molecular subgroups in pancreatic cancer. Clinical pathological features and pathways in each subgroup were also analyzed to find out the potential clinical applications and initial promotive mechanisms of pancreatic cancer. RESULTS: Pancreatic cancer was divided into three subgroups based on different gene expression features. Patients included in each subgroup had specific biological features and responded significantly different to chemotherapy. CONCLUSION: Three distinct subgroups of pancreatic cancer were identified, which means that patients in each subgroup might benefit from targeted individual management.

A Convenient and Sensitive LC-MS/MS Method for Simultaneous Determination of Carbadox- and Olaquindox-Related Residues in Swine Muscle and Liver Tissues.

This paper presents a convenient and sensitive LC-MS/MS method for the simultaneous determination of carbadox and olaquindox residues, including desoxyolaquindox (DOLQ), desoxycarbadox (DCBX), quinoxaline-2-carboxylic acid (QCA), 3-methyl-quinoxaline-2-carboxylic acid (MQCA), and the glycine conjugates of QCA and MQCA (namely, QCA-glycine and MQCA-glycine, resp.) in swine muscle and liver tissues. Tissue samples were extracted with 2% metaphosphoric acid in 20% methanol and cleaned up by solid-phase extraction (SPE) on a mixed-mode anion-exchange column (Oasis MAX). Analysis was performed on a C18 column by detection with mass spectrometry in the multiple reaction monitoring (MRM) mode. The limits of detection (LODs) of the six analytes were determined to be 0.01 µg·kg-1 to 0.25 µg·kg-1, and the limits of quantification (LOQs) were 0.02 µg·kg-1 to 0.5 µg·kg-1. The total recoveries of the six analytes in all tissues were higher than 79.1% with the RSD% less than 9.2%. The developed method can determine the real residue level of QCA and MQCA, whether they are present in free form or as glycine conjugates in tissues, together with the carcinogenic desoxy metabolites DCBX and DOLQ with high recovery. Therefore, this method was suitable for routine analysis of residue control programmes and the residue depletion study of CBX and OLQ on swine.

KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development.

Balanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for brain development, but the underlying mechanisms are not fully understood. Here we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during cortical neurogenesis. Knockdown of KIF20A in NPCs causes dislocation of RGS3 from the intercellular bridge (ICB), impairs the function of Ephrin-B-RGS cell fate signaling complex, and leads to a transition from proliferative to differentiative divisions. Germline and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss of function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial cytokinesis defect or apoptosis. Our results identify a RGS-KIF20A axis in the regulation of cell division and suggest a potential link of the ICB to regulation of cell fate determination.