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Enhanced Effect of miR-148a Targeting STAT3 on Chemosensitivity of Cervical Cancer HeLa Cells to Cisplatin |
| TANG Liangjun1,2, SUN Yan2, ZHANG Xiaohong2, SHENG Shaoqin3 |
1. Graduate School of Zhejiang Chinese Medicine University, Hangzhou 310000, China; 2. Department of Obstetrics and Gynecology, Xuancheng Central Hospital, Xuancheng 242000, China; 3. Department of Obstetrics and Gynecology, Xinhua Hospital Affiliated of Zhejiang Chinese Medicine University, Hangzhou 310000, China
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Abstract Objective To investigate the effect of miR-148a on the chemosensitivity of cervical cancer HeLa cells to cisplatin and its related mechanism. Methods Cervical cancer HeLa cells were cultured in vitro and the concentration gradient of cisplatin was set to detect IC20 value. Control group, mimic control group, miR-148a mimic group, inhibitor control group and miR-148a inhibitor group were set up. qRT-PCR was used to detect the expression of miR-148a and STAT3 mRNA after transfection. After 4 μmol/L cisplatin treatment, the proliferation of HeLa cells was detected by MTT assay; the apoptosis and cell cycle distribution were detected by flow cytometry; Western blot was used to detect the protein expression of p-STAT3/STAT3, CyclinD1, Bcl-2, Bax and Cleaved caspase-3. Results The IC20 of cisplatin on HeLa cells was about 4 μmol/L. Compared with the mimic control group, the level of miR-148a in the miR-148a mimic group was significantly increased, and the level of STAT3 mRNA was significantly decreased (P<0.05). Compared with the inhibitor control group, the level of miR-148a in HeLa cells in miR-148a inhibitor group was significantly decreased, and the level of STAT3 mRNA was significantly increased (P<0.05). On the basis of cisplatin treatment, compared with the mimic control group, the apoptosis rate, G0/G1 phase cell ratio, the protein levels of Bax and Cleaved caspase-3 were significantly increased in miR-148a mimic group, while OD value, the proportions of cells in S and G2/M phase, the protein levels of p-STAT3/STAT3, CyclinD1, Bcl-2 were significantly decreased (P<0.05); compared with the inhibitor control group, the above indicators of HeLa cells in miR-148a inhibitor group changed significantly in the opposite direction (P<0.05). Conclusion MiR-148a could enhance the chemosensitivity of cervical cancer HeLa cells to cisplatin by targetedly inhibiting STAT3.
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Keywords
MicroRNA-148a
Signal transducer and activator of transcription 3
Cervical cancer HeLa cells; Cisplatin
Chemosensitivity
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Fund:Zhejiang Provincial Medical and Health Science and Technology Plan Project (No. 2019KY477); Key Funded Projects of Zhejiang Traditional Chinese Medicine Science and Technology Program (No. 2018ZZ013)
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Issue Date: 18 August 2021
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[1] Li X, Zheng R, Li X, et al. Trends of incidence rate and age at
diagnosis for cervical cancer in China, from 2000 to 2014[J]. Chin
J Cancer Res, 2017, 29(6): 477-486.
[2] Zhuang L, Liu F, Peng P, et al. Effect of Ku80 on the
radiosensitization of cisplatin in the cervical carcinoma cell line
HeLa[J]. Oncol Lett, 2018, 15(1): 147-154.
[3] Dr?gem?ller BI, Brooks B, Critchley C, et al. Further investigation
of the role of ACYP2 and WFS1 pharmacogenomic variants in the
development of cisplatin-induced ototoxicity in testicular cancer
patients[J]. Clin Cancer Res, 2018, 24(8): 1866-1871.
[4] Xu J, Zhang L, Shu G, et al. microRNA-16-5p promotes
3T3-L1 adipocyte differentiation through regulating EPT1[J].
BiochemBiophys Res Commun, 2019, 514(4): 1251-1256.
[5] Kim EA, Kim TG, Sung EG, et al. miR-148a increases the
sensitivity to cisplatin by targeting Rab14 in renal cancer cells[J].
Int J Oncol, 2017, 50(3): 984-992.
[6] 陈元元, 唐铁雷, 程永刚, 等. miR-148a-3p、miR-128、miR-588
在乳腺癌中的表达情况及其与耐药性的关系[J]. 现代肿瘤医
学, 2019, 27(12): 2108-2113. [Chen YY, Tang TL, Cheng YG, et al.
The differential expression of miR-148a-3p, miR-128, miR-588
and their association with chemo-resistance in breast cancer[J].
Xian Dai Zhong Liu Yi Xue, 2019, 27(12): 2108-2113.]
[7] Yao T, Lu R, Zhang J, et al. Growth arrest-specific 5 attenuates
cisplatin-induced apoptosis in cervical cancer by regulating STAT3
signaling via miR-21[J]. J Cell Physiol, 2019, 234(6): 9605-9615.
[8] He M, Xue Y. MicroRNA-148a suppresses proliferation and
invasion potential of non-small cell lung carcinomas via regulation
of STAT3[J]. Onco Targets Ther, 2017, 10: 1353-1361.
[9] Sun H, Fan G, Deng C, et al. miR-4429 sensitized cervical cancer
cells to irradiation by targeting RAD51[J]. J Cell Physiol, 2020,
235(1): 185-193.
[10] Jang SH, Jung YJ, Kim MG, et al. The prognostic significance of
compliance with postoperative adjuvant chemotherapy in patients
with stage III gastric cancer: an observational study[J]. J Gastric
Cancer, 2018, 18(1): 48-57.
[11] Shahid F, Farooqui Z, Khan F. Cisplatin-induced gastrointestinal
toxicity: an update on possible mechanisms and on available
gastroprotective strategies[J]. Eur J Pharmacol, 2018, 827: 49-57.
[12] 文习之, 潘求忠, 翁德胜, 等. 聚乙二醇修饰脂质体阿霉素联
合顺铂单次给药治疗晚期骨肉瘤的剂量递增试验[J]. 中山大
学学报(医学科学版), 2020, 41(4): 582-588. [Wen XZ, Pan QZ,
Weng DS, et al. Pegylated liposomal doxorubicin combined with
cisplatin for advanced osteosarcoma: a single-dose dose-escalating
trial[J]. Zhongshan Da Xue Xue Bao (Yi Xue Ke Xue Ban), 2020,
41(4): 582-588.]
[13] Potestà M, Roglia V, Fanelli M, et al. Effect of microvesicles
from Moringa oleifera containing miRNA on proliferation and
apoptosis in tumor cell lines[J]. Cell Death Discov, 2020, 6: 43.
[14] Du B, Wang X, Wu D, et al. MicroRNA expression profiles identify
biomarkers for predicting the response to chemoradiotherapy in
rectal cancer[J]. Mol Med Rep, 2018, 18(2): 1909-1916.
[15] 李航, 姜勉, 樊赛军. MiR-148a对肺癌细胞放射敏感性的影响[J].
国际放射医学核医学杂志, 2018, 42(3): 248-256. [Li H, Jiang M,
Fan SJ. Effect of miR-148a on the radiosensitivity of lung cancer
cells[J]. Guo Ji Fang She Yi Xue He Yi Xue Za Zhi, 2018, 42(3):
248-256.]
[16] Li B, Wang W, Li Z, et al. MicroRNA-148a-3p enhances cisplatin
cytotoxicity in gastric cancer through mitochondrial fission
induction and cyto-protective autophagy suppression[J]. Cancer
Lett, 2017, 410: 212-227.
[17] 胡轶, 李雄, 蒋桂英, 等. 曲古抑菌素A下调STAT3增强卵巢癌细
胞顺铂化疗敏感性的体外研究[J]. 华中科技大学学报(医学版),
2019, 48(3): 253-257. [Hu Y, Li X, Jiang GY, et al. Tragomycin
A Enhances Chemosensitivity to Cisplatin in Ovarian Cancer Cell
Lines by Down-regulating STAT3[J]. Hua Zhong Ke Ji Da Xue
Xue Bao (Yi Xue Ban), 2019, 48(3): 253-257.]
[18] Wu B, Wang R, Li S, et al. Antifibrotic effects of Fraxetin on
carbon tetrachloride-induced liver fibrosis by targeting NF-κB/
IκBα, MAPKs and Bcl-2/Bax pathways[J]. Pharmacol Rep, 2019,
71(3): 409-416.
[19] Zhang Y, Yang X, Ge X, et al. Puerarin attenuates neurological
deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2
apoptotic pathways in subarachnoid hemorrhage mice[J]. Biomed
Pharmacother, 2019, 109: 726-733.
[20] Zhong Q, Hu Z, Li Q, et al. Cyclin D1 silencing impairs DNA
double strand break repair, sensitizes BRCA1 wildtype ovarian
cancer cells to olaparib[J]. Gynecol Oncol, 2019, 152(1): 157-165.
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