|
|
|
| Expression of miR-30a in gastrointestinal stromal tumors and its mechanism of regulating cell proliferation, invasion and apoptosis |
| REN Hua1 MA Ming1 WANG Chao1 WANG Zhaojun2 |
1.Department of General Surgery, the Fifth People’s Hospital of Datong, Shanxi Province, Datong 037000, China;
2.Department of Physiology, Shanxi Medical University, Shanxi Province, Jinzhong 030600, China |
|
|
|
|
Abstract Objective To observe the expression of microRNA-30a (miR-30a) in gastrointestinal stromal tumors (GIST) and explore its effects on cell biological behaviors and possible mechanisms. Methods Thirty patients with GIST who underwent surgical resection in the Fifth People’s Hospital of Datong from November 2021 to November 2022 were selected as the study object, and the normal tissues removed by surgery (＞ 5 cm away from the edge of GIST tissue) were taken as the control. The expression of miR-30a in GIST tissues and normal tissues was compared. The logarithmic phase GIST-T1 cell line was taken, and the cells transfected with miR-30a negative control plasmid miR-30a NC, overexpression plasmid miR-30a mimics, and silencing plasmid miR-30a inhibitor were set as miR-30a NC group, miR-30a mimics group, and miR-30a inhibitor group, respectively. The cells without treatment were taken as the control group. The proliferation, invasion and apoptosis of each group were detected. The expression of transforming growth factor β1 (TGF-β1), p-Smad2/Smad2 protein were detected. The target relationship between miR-30a and TGF-β1 was verified. Results Compared with normal tissues, the expression of miR-30a in GIST tissues was decreased (P＜0.05). There were no significant differences in proliferation rate at 24, 48 and 72 h, number of transmembrane stained cells, apoptosis rate, TGF-β1 protein expression, and P-Smad2 /Smad2 between miR-30a NC group and control group (P＞0.05). Compared with the control group, the proliferation rate of miR-30a mimics group at 24, 48, 72 h were decreased, the number of stained cells passing through the membrane was reduced, the apoptosis rate was increased, the proliferation rate of miR-30a inhibitor group at 24, 48, 72 h were increased, the number of stained cells passing through the membrane was increased, the apoptosis rate was decreased (P＜0.05). Compared with the control group, the expression of TGF-β1 protein and p-Smad2/Smad2 in miR-30a mimics group was decreased, while those in miR-30a inhibitor group were increased (P＜0.05). Dual luciferase assay showed that TGF-β1 was a target gene of miR-30a. Conclusion The expression of miR-30a in GIST is decreased, which may regulate cell proliferation, invasion and apoptosis by targeting TGF-β signaling pathway.
|
|
|
|
|
|
[1] Sharma AK，Kim TS，Bauer S，et al. Gastrointestinal Stromal Tumor：New Insights for a Multimodal Approach [J]. Surg Oncol Clin N Am，2022，31（3）：431-446.
[2] Schattner A，Glick Y，Sher O，et al. Gastrointestinal stromal tumor of the rectum [J]. Am J Med Sci，2023，365（6）：e99- e101.
[3] Li Y，Ye L，Hu B. Gastric neoplasm：Gastrointestinal stromal tumor mimicking gastric carcinoma [J]. Dig Liver Dis，2021， 53（5）：648-649.
[4] Huang WK，Wu CE，Wang SY，et al. Systemic Therapy for Gastrointestinal Stromal Tumor： Current Standards and Emer- ging Challenges [J]. Curr Treat Options Oncol，2022，23（9）：1303-1319.
[5] Serrano C. New treatments in advanced gastrointestinal stro- mal tumor [J]. Curr Opin Oncol，2021，33（4）：323-328.
[6] Park JW，Jeong JM，Cho KS，et al. MiR-30a and miR-200c differentiate cholangiocarcinomas from gastrointestinal cancer liver metastases [J]. PLoS One，2021，16（4）：e0250083.
[7] Zeng F，You S，Dai X. MiR-30a-5p hampers proliferation of lung squamous cell carcinoma through targeting FBXO45 [J]. Histol Histopathol，2022，37（5）：483-492.
[8] Lin X，Lai X，Feng W，et al. MiR-30a sensitized lung cancer against neoadjuvant chemotherapy by depressing autop- hagy [J]. Jpn J Clin Oncol，2021，51（5）：675-684.
[9] Ding J，Xia Y，Yu Z，et al. Identification of upstream miRNAs of SNAI2 and their influence on the metastasis of gastroin- testinal stromal tumors [J]. Cancer Cell Int，2019，12（19）：289.
[10] Li Y，Ye L，Hu B. Gastric neoplasm： Gastrointestinal stromal tumor mimicking gastric carcinoma [J]. Dig Liver Dis，2021， 53（5）：648-649.
[11] Blay JY，Kang YK，Nishida T，et al. Gastrointestinal stro- mal tumours [J]. Nat Rev Dis Primers，2021，7（1）：22.
[12] H?覬lmebakk T，Wiedswang AM，Meza-Zepeda LA，et al. Inte- grating Anatomical，Molecular and Clinical Risk Factors in Gastrointestinal Stromal Tumor of the Stomach [J]. Ann Surg Oncol，2021，28（11）：6837-6845.
[13] Sharma AK，de la Torre J，IJzerman NS，et al. Location of Gastrointestinal Stromal Tumor （GIST） in the Stomach Pre- dicts Tumor Mutation Profile and Drug Sensitivity [J]. Clin Cancer Res，2021，27（19）：5334-5342.
[14] Bri I，Argyropoulos A，Liegl-Atzwanger B. Update on Mole- cular Genetics of Gastrointestinal Stromal Tumors [J]. Diagnostics （Basel），2021，11（2）：194.
[15] Huang WK，Shi H，Ak?觭akaya P，et al. Imatinib Regulates miR-483-3p and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors [J]. Int J Mol Sci，2021，22（19）：10600.
[16] Huang C，Wang M，Zhao WY，et al. Long noncoding RNA SPRY4-IT1 acts as a miR-101-5p sponge to promote gastrointestinal stromal tumor progression by inhibiting ZEB1 [J]. Am J Transl Res，2023，15（2）：1026-1040.
[17] Qian K，Xu W，Xia X，et al. Methyltransferase-like 3 （METTL3） mediated N6-methyladenosine （m6A） modifications facilitate mir-25-3p maturation to promote gastrointestinal stromal tumors （GISTs） progression [J]. Genes Genomics，2022，44（12）：1519-1530.
[18] Ren Y，Zhang L，Zhang W，et al. MiR-30a suppresses clear cell renal cell carcinoma proliferation and metastasis by targeting LRP6 [J]. Hum Cell，2021，34（2）：598-606.
[19] Cai Y，An B，Yao D，et al. MicroRNA miR-30a inhibits cisplatin resistance in ovarian cancer cells through autophagy [J]. Bioengineered，2021，12（2）：10713-10722.
[20] Chen W，Li Z，Liu H，et al. MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib [J]. Cell Death Dis，2020，11（3）：198.
[21] Wu N，Jiang M，Liu H，et al. LINC00941 promotes CRC metastasis through preventing SMAD4 protein degradation and activating the TGF-β/SMAD2/3 signaling pathway [J]. Cell Death Differ，2021，28（1）：219-232.
[22] Yuan XN，Liu Q，Shao YC，et al. Mettl3 synergistically regulates TGF-β/SMAD2/3 to promote proliferation and meta- stasis of gastric cancer [J]. Am J Cancer Res. 2023，13（7）：3185-3202.
[23] Liang S，Liu Y，He J，et al. Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF- via TGF- promote [J]. Bioengineered，2022， 13（4）：10629-10639.
[24] Song J，Yang P，Li X，et al. Esophageal Cancer-Derived Extracellular Vesicle miR-21-5p Contributes to EMT of ESCC Cells by Disorganizing Macrophage Polarization [J]. Cancers （Basel），2021，13（16）：4122.
[25] Wang S，Xu L，Zhang Z，et al. Overexpressed miR-375- Loaded Restrains Development of Cervical Cancer Through Down-Regulation of Frizzled Class Receptor 4 （FZD4） with Liposome Nanoparticle as a Carrier [J]. J Biomed Nanotechnol，2021，17（9）：1882-1889.
[26] Pourmahdi M，Saber A，Rajabi A，et al. Key Epigenetic Events Involved in the Maintenance of Breast Cancer Stem Cells [J]. Curr Stem Cell Res Ther，2021，16（7）：877-887. |
|
|
|
