1.RP11-789C1.1 inhibits gastric cancer cell proliferation and accelerates apoptosis via the ATR/CHK1 signaling pathway
Wenwei LIU ; Wei FENG ; Yongxin ZHANG ; Tianxiang LEI ; Xiaofeng WANG ; Tang QIAO ; Zehong CHEN ; Wu SONG
Chinese Medical Journal 2024;137(15):1835-1843
Background::Long non-coding RNAs (lncRNAs) plays an important role in the progression of gastric cancer (GC). Their involvement ranges from genetic regulation to cancer progression. However, the mechanistic roles of RP11-789C1.1 in GC are not fully understood.Methods::We identified the expression of lncRNA RP11-789C1.1 in GC tissues and cell lines by real-time fluorescent quantitative polymerase chain reaction. A series of functional experiments revealed the effect of RP11-789C1.1 on the proliferation of GC cells. In vivo experiments verified the effect of RP11-789C1.1 on the biological behavior of a GC cell line. RNA pull-down unveiled RP11-789C1.1 interacting proteins. Western blot analysis indicated the downstream pathway changes of RP11-789C1.1, and an oxaliplatin dosing experiment disclosed the influence of RP11-789C1.1 on the drug sensitivity of oxaliplatin. Results::Our results demonstrated that RP11-789C1.1 inhibited the proliferation of GC cells and promoted the apoptosis of GC cells. Mechanistically, RP11-789C1.1 inhibited checkpoint kinase 1 (CHK1) phosphorylation by binding ataxiatelangiectasia mutated and Rad3 related (ATR), a serine/threonine-specific protein kinase, promoted GC apoptosis, and mediated oxaliplatin sensitivity.Conclusion::In general, we discovered a tumor suppressor molecule RP11-789C1.1 and confirmed its mechanism of action, providing a theoretical basis for targeted GC therapy.
2.Effects of fast-advancing short-term high altitude exposure on different systems in young and middle-aged men
Zehong PENG ; Jianglong WEN ; Wenzhuo ZHU ; Xi ZHU ; Chao LIU ; Heng CHENG ; Qi ZHANG ; Lili ZHU
China Modern Doctor 2024;62(26):15-19
Objective To observe the changes of liver function,blood cell,and lung function of healthy young and middle-aged men before and after fast-advancing short-term high altitude exposure(FSHAE);and to explore the effects and possible mechanisms of FSHAE on the function of liver,blood cells,and lung tissues.Methods This study included 48 healthy young and middle-aged male volunteers,who collected physiological indicators,tested liver function indicators,blood cell indicators,and lung function-related indicators 1 day before entering the plateau(100m above sea level),and 15 days after FSHAE(3000m above sea level).Differences in the relevant parameters of each system were compared before and after FSHAE.Results Compared with those before entering the plateau,the physiological parameters of young and middle-aged men after 15 days of FSHAE heart rate increased significantly,respiratory rate increased,systolic blood pressure increased,mean arterial blood pressure increased,oxygen saturation decreased(P<0.01),and diastolic blood pressure increased(P<0.05),all of which were statistically significant;and the indicators of liver function:glutamic oxaloacetic aminotransferase,glutamic alanine aminotransferase increased(P<0.01),glutamylamine aminotransferase,glutamate aminotransferase,glutaminase,and pulmonary function were increased(P<0.01),glutamyl transpeptidase,alkaline phosphatase,and total bile acids were elevated,and total protein decreased(P<0.05),and the differences were statistically significant.Hemocyte-related indexes:erythrocyte count,erythrocyte pressure volume,mean erythrocyte volume,mean hemoglobin volume,mean hemoglobin concentration,and hemoglobin were elevated,and platelet count decreased(P<0.01),and the differences were statistically significant.although there was an elevation of leukocyte count(P>0.05);Lung function-related indexes:decreased exertion lung volume(P<0.05).There were decreased exertion expiratory volume in the first second,increased one-second rate(P>0.05).Conclusion FSHAE can lead to oxidative stress in the organism,and acute hypoxic multisystemic injury will occur,with the simultaneous emergence of hypoxic adaptive regulation of various systems,self-compensatory repair of various organs of the organism,and there may be the possibility of interactions between various systems.
3.Evaluation of the effect of contrast medium injection in CT enhanced examination of malignant tumor patients with standardized nursing procedure of totally implantable venous power port
Yanli PENG ; Yifan WANG ; Shuli FENG ; Xingping TANG ; Yuanfang LIU ; Yanping LUO ; Xiang ZHANG ; Ming GAO ; Zehong YANG ; Hong DENG
Chinese Journal of Practical Nursing 2024;40(22):1705-1709
Objective:To explore the standardization of totally implantable venous power port of nursing process in CT enhancement and application effect of contrast medium injection, so as to provide a safer and more efficient way for contrast medium injection in CT enhanced examination for patients with malignant tumors.Methods:A non-randomized prospective study was conducted, 358 patients with malignant tumors were selected in Sun Yat-sen Memorial Hospital, Sun Yat-sen University who underwent CT enhanced examination from August 1, 2022 to July 31, 2023, 179 patients who had been implanted totally implantable venous power port were selected as the experimental group, and the standardized nursing procedure was given. The other 179 patients were the control group, using radiology routine high-pressure intravenous indwelling needle as the contrast medium access, with routine peripheral venous nursing process. The incidence of contrast medium extravasation during CT enhanced examination was observed and compared between the two groups.Results:All the patients were included. There were 85 males and 94 females, aged (55.50±11.72) years old in the control group. There were 83 males and 96 females, aged (54.50±12.24) years old in the experimental group. The incidence of contrast medium extravasation was 0 in the experimental group and 3.35%(6/179) in the control group. The difference between the two groups was statistically significant (Fisher exact probability, P<0.05). Conclusions:The application of standardized nursing procedure of totally implantable venous power port to the injection of contrast medium in CT enhanced examination of malignant tumor patients, can significantly reduce the incidence of contrast medium extravasation.
4.Mechanism study of KCMF1 promoting proliferation and NF-κB signaling transduction in colorectal cancer cells
Zhibai WU ; Guiqin XU ; Li ZHANG ; Zhaojuan YANG ; Yun LIU ; Kun JIAO ; Zehong CHEN ; Chen XU ; You ZUO ; Ningqian ZHENG ; Zhiqian YE ; Yongzhong LIU
China Oncology 2024;34(11):987-997
Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P<0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P<0.01),and was positively associated with CRC clinical stage(P<0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P<0.001),induced cell apoptosis(P<0.001),and led to cell cycle arrest in G1 phase(P<0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P<0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P<0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P<0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.
5.A study of the value of three-dimensional T 1WI using different acceleration methods in the application of brain region segmentation
Gang YAO ; Zhuqing ZHOU ; Feng SHI ; Zehong CAO ; Xiaopeng SONG ; Weijun ZHANG ; Wenwen SHEN
Chinese Journal of Radiology 2024;58(10):1006-1014
Objective:To investigate the value of three-dimensional (3D) T 1WI structural images using different acceleration methods including parallel acquisition technique, joint compressed sensing (uCS) technique, and artificial intelligence-assisted compressed sensing (ACS) technique for brain region segmentation. Methods:In this cross-sectional study, fifty patients (female: n=25, age range: 13 to 87 years old) at Corning Hospital of Ningbo University from July to September 2023 were prospectively and consecutively collected. All the subjects underwent brain MRI. Six groups of 3D T 1WI structural images were obtained using different acceleration technique and parameters, including 3D T 1WI without acceleration factor (3D-T 1WI group), 3D T 1WI with parallel acquisition technique with acceleration factor 3 (3D-T 1WI-PI-3 group), 3D T 1WI with uCS technique with acceleration factor 4.5 and 6.9 (3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group), 3D T 1WI by ACS technique with acceleration factors of 3 and 5 (3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group). T 2WI fluid-attenuated inversion recovery (FLAIR) images were also acquired. Subjective scores (cerebral grey matter and white matter clarity scores, clarity scores of cerebral white matter degeneration lesions in relation to the surrounding white matter, and Gibbs artifact scores) and objective metrics [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), cerebrospinal fluid signal homogeneity, peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and natural image quality evaluator (NIQE)] were used to evaluate image quality in different groups. Totally 109 brain regions were segmented and volumes were measured using the uAI Research Portal image analysis tool. Kappa or intraclass correlation coefficient ( ICC) was used to evaluate the agreement of subjective and objective evaluation indexes between the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group, and 3D-T 1WI group. Kappa or ICC value>0.70 was considered as good agreement. Results:The acquisition time for the 3D-T 1WI group, 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group were 527, 204, 169, 95, 133, 90 s, respectively. Subjective evaluation showed that the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups had excellent agreement with the 3D-T 1WI group in terms of the distribution of cases of cerebral grey matter and white matter clarity scores, respectively (all Kappa value=1.000); The distribution of cases of clarity score of cerebral white matter lesions and surrounding white matter in the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group were in good agreement with that of the 3D-T 1WI group ( Kappa values of 0.775, 0.701, and 0.777, respectively); the distribution of the number of cases of the Gibbs artifact score of the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups was in good agreement with the 3D-T 1WI group (all Kappa value=1.000). Objective evaluation showed the CNR of the images in the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, and 3D-T 1WI-uCS-6.9 groups were in good agreement with those of the 3D-T 1WI group ( ICC of 0.720, 0.759, and 0.752, respectively); PSNR and SSIM were in good agreement among the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group (PSNR: ICC=0.854; SSIM: ICC=0.851). NIQE of 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group images were in good agreement with the 3D-T 1WI group ( ICC value of 0.866, 0.727, 0.753, respectively). The ICC values of the volume of each segmented brain region among the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, 3D-T 1WI-uCS-6.9, 3D-T 1WI-ACS-3, 3D-T 1WI-ACS-5 group and the 3D-T 1WI group images showed decreased in order (all ICC≥0.62). Conclusions:The uCS and ACS techniques used in 3D-T 1WI show high agreement with 3D-T 1WI in terms of brain segmentation. The application of these accelerating techniques can significantly shorten the acquisition time with obtaining images with good image quality, displaying great value.
6.Effects of fasudil hydrochloride on ROCK2 protein and ferroptosis in hippocampus during early brain injury in rats with subarachnoid hemorrhage
Linlin SUN ; Zhiying LI ; Xingxiang ZHANG ; Zehong XU ; Baiqiang WU ; Tiantian WANG ; Xinge XU ; Aijun FU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):9-14
Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.
7.Research on the motivation of young patients′ medical electronic word-of-mouth sharing on internet platforms
Jingjing XIONG ; Shiyi WANG ; Xingyue YU ; Fengzhuo YANG ; Ziyi MAO ; Jintong ZOU ; Zehong ZHANG
Chinese Journal of Hospital Administration 2023;39(4):310-315
Objective:To explore the facilitating and inhibitory factors influencing the behavior of young patients to share medical electronic word-of-mouth (eWOM) on internet platforms, so as to provide insights for the improvement of healthcare quality.Methods:In May 2022, 271 undergraduate students from universities in Zhejiang province were selected by convenient sampling to survey their motivations to share eWOM with a self-designed questionnaire. Multiple regression analysis was used to examine the impact of different motivational factors on the sharing intention of young patients.Results:Only 16 respondents (5.9%) had previously published medical eWOM. Egoistic motivation, altruistic motivation, medical experience, and comment habits were significant factors that promoted patients to share eWOM, with egoistic motivation ( β=0.212, P<0.001) having the greatest impact and comment habit ( β=0.139, P=0.003) having the least impact. Distrust, low self-efficacy and involvement, perceived reluctance, and perceived uselessness were significant factors inhibiting patients from publishing eWOM. Of them, distrust ( β=-0.161, P<0.001) and perceived reluctance ( β=-0.161, P=0.001) had the greatest impact, and low self-efficacy and involvement had the least impact ( β=-0.134, P=0.003). Conclusions:To enhance the positive attitude of young patients towards sharing eWOM, it is important to focus on their personal benefits and provide high-quality healthcare experiences. Building trust among patients in the platform is crucial, and efforts should be made to reduce operational barriers. Additionally, educating and raising awareness among young patients regarding the significance and influence of healthcare reviews is important.
8.Analysis of influencing factors for ultrasonic missed diagnosis of kidney neoplasm
Zehong SHI ; Shaoling YUAN ; Xinyang GUO ; Yan ZHANG
Cancer Research and Clinic 2023;35(12):934-938
Objective:To investigate the influencing factors of ultrasonic missed diagnosis of kidney neoplasm.Methods:The clinical data of 2 033 patients pathologically diagnosed with kidney neoplasm after operation and with complete medical record in Shanxi Province Cancer Hospital from January 2013 to October 2021 were retrospectively analyzed. Preoperative ultrasound diagnosis, clinical data, CT/magnetic resonance imaging (MRI) were analyzed, and ultrasound missed diagnosis rate was calculated. Chi-square test and multivariate logistic regression were used to analyze the influencing factors of ultrasonic missed diagnosis of kidney neoplasm mainly based on the anatomic characteristics of neoplasm.Results:The ultrasonic missed diagnosis rate of kidney neoplasm was 1.87% (38/2 033), among which the ultrasonic missed diagnosis rate of renal parenchymal neoplasm was 1.33% (25/1 874) and the ultrasonic missed diagnosis rate of renal pelvis neoplasm was 8.18% (13/159). The results of multivariate logistic regression analysis showed that the patients' body mass index (BMI) ≥ 24 kg/m 2 ( OR = 2.805, 95% CI 1.030-7.641), the small lesion ( OR = 0.425, 95% CI 0.293-0.617), the lesion located on the left kidney ( OR = 0.307, 95% CI 0.113-0.834), the lesion located on the body ( OR = 0.344, 95% CI 0.124-0.956 compared to lesions in the upper pole of the kidney; OR = 0.239, 95% CI 0.069-0.834 compared to lesions in the lower pole of the kidney) and the lesion located on the dorsal side ( OR = 0.409, 95% CI 0.172-0.970) were independent influencing factors for ultrasound missed diagnosis of renal parenchymal neoplasms (all P < 0.05). Patients with BMI ≥ 24 kg/m 2 ( OR = 10.464, 95% CI 1.042-105.087), concurrent ureteral or (and) bladder urothelial carcinoma ( OR = 32.937, 95% CI 4.017-270.063), and small lesion size ( OR = 0.216, 95% CI 0.081-0.577) were independent influencing factors for ultrasound missed diagnosis of renal pelvis neoplasms (all P < 0.05). Conclusions:Obesity, small focus, focus on the left kidney, focus on the body, and focus on the back may be the main reasons for ultrasonic missed diagnosis of renal parenchymal neoplasms. Obesity, concurrent ureteral or/and bladder urothelial carcinoma and small lesions may be the main reasons for ultrasonic missed diagnosis of renal pelvis neoplasms.
9.Septic shock following ultrasound-guided suprapubic puncture cystostomy: a case report
Qiang GUO ; Xi ZHANG ; Chengyong LI ; Zehong AO ; Chuan HAO
Chinese Journal of Urology 2023;44(12):945-946
A case is presented involving a patient with a history of pelvic fracture who experienced progressive difficulty in urination following the removal of a urethral catheter. Attempt to retain the catheter was unsuccessful, leading to an ultrasound-guided suprapubic puncture cystostomy. Subsequently, the patient developed persistent abdominal pain, distension, nausea, and vomiting. Analysis of turbid greyish-yellow thin purulent fluid obtained during abdominal paracentesis indicated the presence of peritonitis. Urgent surgical exploration revealed that the diversion tube had passed through the abdominal cavity and into the bladder. The entire abdominal cavity was filled with yellowish-thin purulent fluid. Intraoperatively, the patient presented with worsening hypotension, tachycardia, oliguria, and decreased skin temperature, suggestive of septic shock resulting from peritonitis. Prompt management, including antimicrobial therapy, hemodynamic support, and fluid resuscitation, successfully controlled the infectious symptoms, leading to complete recovery. In clinical practice, the emphasis is often placed on assessing injuries to intra-abdominal organs, whereas awareness and understanding of peritoneal injuries remain limited. As a result, postoperative peritonitis is frequently attributed solely to intra-abdominal organ damage, overlooking the potentially grave consequences of pure peritoneal injury. Therefore, it is imperative to enhance our recognition and knowledge regarding peritoneal injuries, enabling timely diagnosis and treatment to prevent the occurrence of complications.
10.Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.
Yixian CUN ; Sanqi AN ; Haiqing ZHENG ; Jing LAN ; Wenfang CHEN ; Wanjun LUO ; Chengguo YAO ; Xincheng LI ; Xiang HUANG ; Xiang SUN ; Zehong WU ; Yameng HU ; Ziwen LI ; Shuxia ZHANG ; Geyan WU ; Meisongzhu YANG ; Miaoling TANG ; Ruyuan YU ; Xinyi LIAO ; Guicheng GAO ; Wei ZHAO ; Jinkai WANG ; Jun LI
Genomics, Proteomics & Bioinformatics 2023;21(4):707-728
Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).
Humans
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Cell Line, Tumor
;
Cell Proliferation
;
Gene Expression Regulation, Neoplastic
;
Glioblastoma/genetics*
;
Methyltransferases/metabolism*
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RNA Splicing Factors/metabolism*
;
RNA, Messenger/genetics*
;
RNA-Binding Proteins/metabolism*
;
Serine-Arginine Splicing Factors/metabolism*
;
RNA Methylation/genetics*

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