Over-activation of EFTUD2 correlates with tumor propagation and poor survival outcomes in hepatocellular carcinoma

PurposeElongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study.MethodsBioinformatic analysis was performed to find differential expressed genes and related pathways. Western blotting and quantitative PCR assays were used to verify the EFTUD2 expression in HCC cell lines and tumor tissues of liver cancer patients. Transfection of shRNAs in SKHEP1 and Huh7 cell lines was conducted to explore the mechanisms of EFTUD2 in HCC. CCK-8 method, colony formation, and cell cycle detection kit were used to detect the proliferation. A tumor model in nude mice was used to explore the role of EFTUD2 in liver cancer in vivo.ResultsBased on the tumor tissues and para-tumor tissues in our HCC patients, we identified EFTUD2 as highly expressed in HCC tissues (P < 0.001). Bioinformatic analysis from the TCGA database also supported this biological phenomenon (P = 1.911e−17). Furtherly, the results of clinical specimens and TCGA data suggested that higher EFTUD2 expression levels correlated with high histologic grades, high pathological grades, and poor survival prognoses in HCC patients. And knockdown of EFTUD2 suppressed cell proliferation and colony formation in vitro. In vivo, knockdown of EFTUD2 constrained the tumor growing and expansion derived from SKHEP1 cells and induced a decrease in the tumor volume and tumor weight resected from nude mice. Furthermore, RNA sequencing based on EFTUD2 knockdown revealed that EFTUD2 affected target genes concerned with the cell cycle. Flow cytometric analyses in the SKHEP1 cell model revealed that knockdown significantly suppressed cell cycle course and caused cell cycle arrest in the G1 phase. CyclinD1 proteins were also inhibited by knocking down of EFTUD2.

Over-activation of EFTUD2 correlates with tumor propagation and poor survival outcomes in hepatocellular carcinoma.

PURPOSE: Elongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study. METHODS: Bioinformatic analysis was performed to find differential expressed genes and related pathways. Western blotting and quantitative PCR assays were used to verify the EFTUD2 expression in HCC cell lines and tumor tissues of liver cancer patients. Transfection of shRNAs in SKHEP1 and Huh7 cell lines was conducted to explore the mechanisms of EFTUD2 in HCC. CCK-8 method, colony formation, and cell cycle detection kit were used to detect the proliferation. A tumor model in nude mice was used to explore the role of EFTUD2 in liver cancer in vivo. RESULTS: Based on the tumor tissues and para-tumor tissues in our HCC patients, we identified EFTUD2 as highly expressed in HCC tissues (P < 0.001). Bioinformatic analysis from the TCGA database also supported this biological phenomenon (P = 1.911e-17). Furtherly, the results of clinical specimens and TCGA data suggested that higher EFTUD2 expression levels correlated with high histologic grades, high pathological grades, and poor survival prognoses in HCC patients. And knockdown of EFTUD2 suppressed cell proliferation and colony formation in vitro. In vivo, knockdown of EFTUD2 constrained the tumor growing and expansion derived from SKHEP1 cells and induced a decrease in the tumor volume and tumor weight resected from nude mice. Furthermore, RNA sequencing based on EFTUD2 knockdown revealed that EFTUD2 affected target genes concerned with the cell cycle. Flow cytometric analyses in the SKHEP1 cell model revealed that knockdown significantly suppressed cell cycle course and caused cell cycle arrest in the G1 phase. CyclinD1 proteins were also inhibited by knocking down of EFTUD2. CONCLUSION: EFTUD2 is markedly overexpressed in HCC tumor tissues. High EFTUD2 expression in HCC patients is associated with clinical features. Moreover, we confirmed that EFTUD2 shows a pivotal role in HCC cell proliferation and cell cycle course and could be a possible therapeutic avenue in HCC through disturbing EFTUD2.

[Surveillance and response to measles outbreaks in China, 2016-2020].

Objective: To understand the epidemiological characteristics of measles outbreaks in China from 2016 to 2020 and related outbreak investigations and response performances. Methods: The information about the incidence of measles outbreaks, the investigation and response of measles outbreaks in 31 provinces from 2016 to 2020 were collected from Measles Surveillance System, and the incidence of suspected measles outbreaks detected through sporadic case finding during the same period according to the measles outbreak definition was analyzed. Results: From 2016 to 2020, a total of 344 measles outbreaks were reported nationwide, involving 1 886 measles cases. The median of intervals between the first case onsets and reported outbreaks ranged from 4 to 10 days, the median of the numbers of involved cases ranged from 2 to 3, and the median of the duration of the epidemic ranged from 8 to 13 days, and some outbreaks had long durations of 65,44,28,63 and 13 days. The top three provinces with high number of reported outbreaks were Gansu, Beijing and Shandong. Among the reported outbreaks, 115 occurred in communities/villages, accounting for the highest proportion. The genotype identification results indicated that all the outbreaks in 2016 were caused by measles virus H1, and the proportion of the outbreaks caused by measles virus H1 decreased year by year since then, which was 88.57% (31/35) in 2017, 85.00% (17/20) in 2018 and 15.79% (3/19) in 2019 respectively. There was no outbreak caused by measles H1 reported in 2020, the 4 isolates all belonged to genotype D8. Active case findings were conducted in local medical institutions for 313 outbreaks, and measles-containing vaccine coverage surveys were conducted for 266 outbreaks. From 2016 to 2020, a total of 919 suspected measles outbreaks were detected nationwide, involving 4 212 measles cases. The top three provinces with suspected measles outbreaks were Xinjiang, Gansu and Sichuan. The suspected measles outbreaks also mainly occurred in communities/villages (493). Conclusions: The number, scale and duration of measles outbreaks were gradually decreasing, the measles outbreaks at the community level can not be ignored, and the local H1 genotypes tend to be gradually replaced by other genotypes. Improving the sensitivity of outbreak surveillance, promoting vaccination, expanding the vaccine coverage, timely and effective response to the outbreaks are the focus of measles elimination in China in the future.

[Epidemic profile of mumps in China during 2004-2013].

OBJECTIVE: To analyze the epidemiological characteristics of mumps in China from 2004 to 2013. METHODS: Data of mump cases occurring between 2004 and 2013 were gathered from the national notifiable disease reporting system in China (excluding Hong Kong, Macao, and Taiwan); only cases classified as "final card" , laboratory confirmed, or clinical diagnosis were included. Descriptive epidemiology techniques were used to analyze features of sex, age, trends over time, and geography. RESULTS: Average incidence of mumps between 2004 to 2013 was 24.20/100 000. Peaks were in 2011 and 2012, with incidence 33.9/100 000 (454 385/1.340 million) and 35.6/100 000 (479 518/1.347 million). Two seasonal peaks occurred regularly in years, one from April to July in the first year, and the other from November to January in the next year. During the study period, provinces with the highest incidence were Ningxia, Tibet, Xinjiang, and Guangxi; incidences were 72.1/100 000 (4 425/6.13 million), 48.5/100 000 (1 396/3 million), 51.7/100 000 (10 887/21.04 million), and 40.8/100 000 (19 179/46.99 million), respectively. Guangdong (28 078), Sichuan (21 924), Guangxi (21 616), and Zhejiang (20 000) provinces reported the highest number of mumps cases. Beijing, Tianjin, and Shanghai showed a consistently low incidence. Mumps cases occurred primarily among children aged 5-9 years, with incidence ranging from 118.2/100 000 to 281.4/100 000. In 2004-2008, the peak age was 6-8 years (174.1/100 000) and in 2009-2013, peak age was 5-7 years (234.5/100 000). CONCLUSION: The highest incidences of mumps in China were reported in 2011 and 2012, with children of school age constituting the majority of cases.

[Spatial autocorrelation analysis of measles in China, 2005-2014].

OBJECTIVE: To detect the spatial features of measles in China by means of spatial statistical analysis. METHODS: Data of prefecture-level measles cases and incidence from 2005 to 2014 were collected from the China Information System for Disease Control and Prevention. Information collected from the system included demographic characteristics, spatial distribution information, and diagnostic reports. Cases of unconfirmed measles and those with unknown address were ruled out. Cases from Hong Kong, Macao, Taiwan, and foreign countries were not included in this study. Maps were obtained from geographical boundary data at prefecture level from the Chinese Center for Disease Control and Prevention and demographic data from the National Bureau of Statistics. Based on different measures of measles elimination, we divided the data from 2005 to 2014 into three stages: stage 1 (2005-2008), stage 2 (2009-2012), and stage 3 (2013-2014). ArcGIS software was used to describe the spatial distribution and for global and local spatial autocorrelation analysis. RESULTS: The total number of confirmed measles cases reported in the system was 650 222, with average incidence 0.46/100 000. The highest reported incidence was in 2008 (9.95/100 000) and the lowest in 2012 (0.46/100 000). Average incidences for stages 1, 2, and 3 were 8.87/100 000, 1.99/100 000 and 2.96/100 000, respectively. Global Moran's I coefficients from 2005 to 2014 were 0.31, 0.08, 0.36, 0.56, 0.26, 0.48, 0.34, 0.20, 0.29 and 0.52, respectively; all were significant (P<0.05). Average incidences for high-high (H-H) clusters in 2005-2008, 2009-2012, and 2013-2014 were 33.02/100 000, 7.06/100 000, 11.91/100 000, respectively. Western China had high-value clustering consistently throughout all three periods; however, the number of prefectures covered by high-value clusters and discrepancy in the incidence between western and eastern regions were low. Northeast and northern China had H-H clustering in stages 2 and 3. CONCLUSION: In this study, measles incidence was spatially autocorrelated at the prefecture level from 2005 to 2014. Although China has made great progress in the elimination of measles, H-H clusters were consistently present. A need remains in China for targeted measles prevention and control measures.