1.Analysis of the demands for pharmaceutical clinic service and influential factors based on Kano model
Han SHAN ; Xuan YE ; Zihan GUO ; Jing WU ; Jinwei HU ; Xiaopei TONG ; Yufei BIN ; Jiyong LIU ; Qiong DU ; Mengmeng WANG
China Pharmacy 2025;36(22):2850-2855
OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands, providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted, and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services, while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender, age, educational attainment, and economic burdens, to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%, yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware (P<0.001). The demand for pharmaceutical clinic services exhibited a hierarchical characteristic: twelve items were identified as attractive attributes (e. g., providing suggestions for more affordable treatment options, offering online consultation services, etc.), five items as expected attributes (e.g., having a good attitude and being able to patiently answer your questions, etc.), three items as must-have attributes (e.g., providing guidance on medication dosage and usage, providing guidance on medication precautions, etc.), five items as indifferent attributes (e.g., providing treatment plan recommendations based on the patient’s condition). There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients (P<0.001); patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above (P=0.016); those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above (P=0.011); patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” (P=0.002). CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low; however, those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover, the study also revealed that factors such as gender, age, educational level, and economic burdens exert significant influences on patients’ service demands.
2.Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.
Zihan WANG ; Kaige ZHANG ; Minghao HUANG ; Dehao SHANG ; Xiaomin HE ; Zhou WU ; Xu YAN ; Xinwen ZHANG
Acta Pharmaceutica Sinica B 2025;15(6):2966-2984
Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.
3.Synergistic strategies of scaffold construction and drug delivery systems for cartilage regeneration.
Qiyao ZHANG ; Pei FENG ; Zihan PEI ; Yinsheng CAO ; Kun JIANG ; Xiong CAI ; Ping WU
Chinese Journal of Biotechnology 2025;41(8):3049-3063
In recent years, the rapid development of transportation and sports industries, coupled with the accelerated population aging in China, has led to a steady increase in the incidence of articular cartilage injuries, wear, and degenerative changes. Currently, the clinical treatment options for cartilage defects primarily include conservative therapies and surgical interventions, both of which have certain limitations. Cartilage tissue engineering (CTE), as a novel technology, provides an infinite prospect for cartilage regeneration and repair. Because of the abilities of scaffolds to mimic the natural cartilage structure, exhibit excellent biocompatibility and biomimetic mechanical properties, and promote cell adhesion and proliferation, scaffolds are considered effective delivery systems for growth factors, genes, and drugs. This review summarizes the clinical treatments for cartilage defects and their limitations, discusses the materials and preparation techniques of scaffolds used in CTE, with a particular focus on drug-loaded scaffold delivery systems in cartilage repair and regeneration, and offers a perspective on the future application of drug-loaded CTE. The aim is to provide theoretical guidance and new approaches for the repair of cartilage defects.
Tissue Engineering/methods*
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Humans
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Tissue Scaffolds
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Drug Delivery Systems/methods*
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Regeneration
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Cartilage, Articular/physiology*
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Animals
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Biocompatible Materials
4.Comparison of safety and efficacy of robot assistance versus conventional freehand methods in the upper cervical spine surgery
Jian CHEN ; Qingqing LI ; Shujie ZHAO ; Mengyuan WU ; Zihan ZHOU ; Jiayun LIU ; Peng GAO ; Jin FAN ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Guoyong YIN ; Wei ZHOU
Chinese Journal of Orthopaedics 2024;44(8):578-586
Objective:To evaluate the impact of orthopedic robotic assistance and conventional freehand methods on surgical strategies, the safety of pedicle screw placement, and clinical efficacy in patients with upper cervical spine diseases.Methods:From January 2017 to March 2023, a total of 63 cases with upper cervical spine disease, were divided into two groups based on the screw placement technique: the robot-assisted pedicle screw placement (RA) group (41 cases) and the conventional freehand pedicle screw placement (CF) group (22 cases), were retrospectively included. These patients in the RA and CF groups underwent two types of posterior cervical surgery, including occipitocervical fusion (9 cases and 8 cases) and fixation and fusion of atlantoaxial and distal vertebrae (32 cases and 14 cases). The outcome parameters, including the disease course, surgical time, intraoperative blood loss, fluoroscopy frequency, radiation dose, hospital stay, treatment costs, complications, the rate of the pedicle screw placement, accuracy of upper cervical pedicle screw placement, and the risk factors that possibly affected the accuracy were recorded and analyzed. Postoperative follow-up was conducted for at least 6 months, and the efficacy of patients was assessed using imaging parameters, ASIS classification, VAS, and JOA scores.Results:Both groups had no screw-related complications and no spinal cord or vertebral artery injuries. In the RA group, the pedicle screw placement rates for the patients with occipitocervical fusion, and fixation and fusion of atlantoaxial and distal vertebrae were 100% (48/48) and 89.6% (138/154), respectively, far exceeding the placement rate in the CF group 42.9% (18/42) and 78.3% (54/69) (χ 2=37.403, P<0.001; χ 2=5.128, P=0.024). The fluoroscopic exposure dose and operation time of the two types of surgical patients in the RA group were both higher than those in the CF group ( P<0.05). Compared with the CF group, the accuracy of C 1 screws in the RA group increased from 42% (11/26) to 80% (51/64), with statistical significance (χ 2=13.342, P=0.004); while the accuracy of C 2 screws improved from 77% (33/43) to 88% (63/72) with no statistical difference (χ 2=2.863, P=0.413). Non-parametric correlation analysis found a significant correlation between the accuracy of C 1 and C 2 pedicle screw placement and the order of guide wire insertion in the RA group ( r=0.580, P<0.001; r=0.369, P=0.001). Postoperatively, both groups showed significant differences in cervicomedullary angle (CMA), Chamberlain angle (CL), McGregor angle, Boogard angle, Bull angle, clivus-canal angle (CCA), occipitocervical (C 0-C 2) angle, posterior occipitocervical angle (POCA), C 2-C 7 angle, and anterior atlantodental interval (ADI) ( P<0.05). The ASIA classification improved to varying degrees for both groups postoperatively, but there were no statistically significant differences between preoperative, postoperative, and last follow-up evaluations. VAS and JOA scores significantly improved for both groups postoperatively and at the last follow-up ( P<0.05). Conclusion:Both orthopedic robotic-assisted and conventional freehand pedicle screw placement techniques achieved satisfactory therapeutic effects in the treatment of upper cervical spine diseases. The orthopedic robot can effectively ensure the accuracy of upper cervical pedicle screw placement, the increase placement rate of pedicle screws in the upper cervical spine, and reduce fluoroscopy exposure. However, it is necessary to avoid the vertebral displacement caused by the priority insertion of the guide needle, which may affect the accuracy of subsequent planning.
5.Influence of maternal autoimmune diseases and anticoagulants on fetal fraction of maternal plasma cell-free DNA
Xuemei CHEN ; Honglei DUAN ; Wanjun WANG ; Ying ZHANG ; Xiangyu ZHU ; Xing WU ; Ying YANG ; Peixuan CAO ; Mengyao NI ; Zihan JIANG ; Biyun XU ; Jie LI
Chinese Journal of Perinatal Medicine 2024;27(6):450-456
Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=-0.423), conceived by assisted reproductive technology ( B=-0.803), male fetus ( B=-0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=-0.415), conceived by assisted reproductive technology ( B=-0.585), male fetus ( B=-0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.
6.Comparison of clinical outcomes of forearm radial flap and anterolateral thigh flap for repairing soft tissue defects after oral cancer resection
Jiang ZHU ; Wushuang XU ; Zihan MA ; Yucheng XIANG ; Wanying SHI ; Senbin WU ; Donghui SONG
Chinese Journal of Plastic Surgery 2024;40(9):992-1001
Objective:To compare the efficacy of radial forearm flap and anterolateral thigh flap in repairing soft tissue defects after oral cancer surgery and to explore their indications.Methods:A retrospective analysis was conducted on clinical data of patients with oral cancer treated at the Department of Stomatology, Affiliated Hospital of Nantong University, from May 2019 to February 2023. Patients were divided into two groups based on the repair method: the radial forearm flap group and the anterolateral thigh flap group. The groups were compared in the following aspects. (1) Surgical parameters including defect area after oral cancer resection, flap area, flap preparation time, operation time, and length of hospital stay. (2) Inflammatory markers (interleukin-6 and C-reactive protein levels) measured 1 day before surgery and 1 day after surgery. (3) Flap survival rate was calculated. (4) Complication rates was calculated in the flap donor area and infection rates in the oral recipient area within 6 months postoperatively. (5) Six months postoperatively, the patient’s oral function was assessed by a physician using the University of Washington quality of life scale (UW-QOL). The evaluation included assessments of oral opening, speech, and eating functions. Each parameter was scored on a scale of 0 to 10 (higher scores indicated better recovery). (6) Quality of life was assessed using the 36-item short form health survey scale(SF-36) at 2, 4 and 6 months postoperatively, with scores ranging from 0 to 100 (higher scores indicated better quality of life). (7) Patient satisfaction was assessed at 6 months postoperatively, with satisfaction levels categorized as satisfied, basically satisfied, and dissatisfied. The satisfaction rate was calculated as (satisfied + basically satisfied ) cases / total cases in each group × 100%. Statistical analysis was performed using SPSS 22.0. Measurement data were expressed as Mean±SD, and comparisons between groups were conducted using t-tests. Count data were expressed as cases and (or) percentages, and comparisons were made using chi-square test. P<0.05 was considered statistically significant. Results:The radial forearm flap group included 48 cases (32 males, 16 females), aged (49.3±5.0) years, with a body mass index (BMI) of (23.0±1.1) kg/m 2 and a disease course of (6.5±2.1) months. The group had 21 cases of tongue cancer, 12 of floor of mouth cancer, and 15 of buccal cancer, including 40 squamous cell carcinomas and 8 basal cell carcinomas. The anterolateral thigh flap group included 32 cases (20 males, 12 females), aged (50.1±5.0) years, with a BMI of (23.0±1.0) kg/m 2 and a disease course of (7.0±2.2) months. The group had 16 cases of tongue cancer, 7 cases of floor of mouth cancer, and 9 cases of buccal cancer, including 27 squamous cell carcinomas and 5 basal cell carcinomas. There were no significant differences in gender, age, BMI, disease course, tumor location, or pathological type between the two groups ( P>0.05). The defect area after oral cancer resection was smaller in the radial forearm flap group[ (39.0±1.3) cm 2 ] compared to the anterolateral thigh flap group[ (40.3±2.2) cm 2] ( t=3.32, P=0.001). There were no significant differences in flap area, flap preparation time, or length of hospital stay between the two groups ( P>0.05). The operation time was shorter in the radial forearm flap group [(5.1±1.1) h] compared to the anterolateral thigh flap group [(6.8±2.8) h] ( t=0.26, P<0.001). There were no significant differences in interleukin-6 and C-reactive protein levels between the two groups 1 day before surgery and 1 day after surgery ( P>0.05). The flap survival rates were 97.9% (47/48) in the radial forearm flap group and 93.8% (30/32) in the anterolateral thigh flap group, with no significant difference( P>0.05). Postoperative donor site complications mainly included infection, pigmentation, itching, etc. The overall incidence of complications in the donor site of the radial forearm flap [33.3% (16/48)] was higher than that in the anterolateral thigh flap group [12.5% (4/32)], and the difference was statistically significant ( χ2=4.44, P=0.035). There was no significant difference in infection rates in the oral recipient area between the two groups ( P>0.05). Six months postoperatively, the average scores for oral opening, speech, and eating functions were above 7 in both groups, with no significant differences ( P>0.05). Quality of life scores improved over time in both groups, with average scores above 90 at 6 months postoperatively, and no significant differences at any time point ( P>0.05). The patient satisfaction rate was 91.7% (44/48) in the radial forearm flap group and 90.6% (29/32) in the anterolateral thigh flap group, with no significant difference ( P>0.05). Conclusion:Both radial forearm flap and anterolateral thigh flap can effectively repair soft tissue defects after oral cancer resection, significantly improving patients’oral function. The anterolateral thigh flap provides sufficient tissue volume and is suitable for patients with larger defect areas. The radial forearm flap is suitable for patients with a smaller defect area after oral cancer resection. Its surgical procedure is relatively less complex and offers an advantage in reducing surgery time. However, the donor site complications are higher with the radial forearm flap compared to the anterolateral thigh flap.
7.Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway
Lei WANG ; Fenlan BIAN ; Feiyang MA ; Shu FANG ; Zihan LING ; Mengran LIU ; Hongyan SUN ; Chengwen FU ; Shiyao NI ; Xiaoyang ZHAO ; Xinru FENG ; Zhengyu SUN ; Guoqing LU ; Pinfang KANG ; Shili WU
Journal of Southern Medical University 2024;44(10):1955-1964
Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.
8.LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway
Xirui FAN ; Zhilin QI ; Yuanjie DENG ; Zihan YANG ; Li SUN ; Guohao LI ; Juanjuan LIANG ; Fei WU ; Liwen YUAN
Journal of Southern Medical University 2024;44(10):2033-2043
Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.
9.Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway
Lei WANG ; Fenlan BIAN ; Feiyang MA ; Shu FANG ; Zihan LING ; Mengran LIU ; Hongyan SUN ; Chengwen FU ; Shiyao NI ; Xiaoyang ZHAO ; Xinru FENG ; Zhengyu SUN ; Guoqing LU ; Pinfang KANG ; Shili WU
Journal of Southern Medical University 2024;44(10):1955-1964
Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.
10.LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway
Xirui FAN ; Zhilin QI ; Yuanjie DENG ; Zihan YANG ; Li SUN ; Guohao LI ; Juanjuan LIANG ; Fei WU ; Liwen YUAN
Journal of Southern Medical University 2024;44(10):2033-2043
Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.

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