LncRNA PCAT-1 Reduces Sensitivity of Cervical Carcinoma Cells to Cisplatin by Regulating STAT3 and PTEN Expression

MAO Xuebao; WANG Xiuhong

doi:10.3971/j.issn.1000-8578.2021.21.0148

Cancer Research on Prevention and Treatment > 2021 > 48(9): 833-838. > DOI: 10.3971/j.issn.1000-8578.2021.21.0148

MAO Xuebao, WANG Xiuhong. LncRNA PCAT-1 Reduces Sensitivity of Cervical Carcinoma Cells to Cisplatin by Regulating STAT3 and PTEN Expression[J]. Cancer Research on Prevention and Treatment, 2021, 48(9): 833-838. DOI: 10.3971/j.issn.1000-8578.2021.21.0148

Citation:

PDF (3594 KB)

LncRNA PCAT-1 Reduces Sensitivity of Cervical Carcinoma Cells to Cisplatin by Regulating STAT3 and PTEN Expression

Department of Gynecology, The Center Hospital of Xianning City, The First Affiliated Hospital of Hubei College of Science and Technology, Xianning 437100, China

More Information

Received Date: February 04, 2021
Revised Date: July 11, 2021
Available Online: January 12, 2024

Graphical Abstract

Abstract

Abstract

Objective
To investigate the role and regulatory mechanism of lncRNAs PCAT-1 in the sensitivity of cervical cancer cells to DDP.
Methods
The expressions of PCAT-1 in human cervical cancer cell lines (HeLa and SiHa) and DDP-resistant cell lines (HeLa/DDP and SiHa/DDP) were analyzed by real-time PCR. After PCAT-1 silencing and overexpression in HeLa/DDP and SiHa/DDP cells, CCK-8 and flow cytometry were used to detect cell viability ability and cell cycle, respectively. Western blot was used to detect the protein expression of STAT3 and PTEN.
Results
The DDP resistance index of HeLa/DDP cells to HeLa cells was 4.49, while that of SiHa/DDP cells to SiHa cells was 6.87. The expression levels of PCAT-1 in HeLa/DDP and SiHa/DDP cells were significantly higher than those in HeLa and SiHa cells, respectively (P < 0.05). The overexpression of PCAT-1 reduced the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP, enhanced the proportion of S phase in cell cycle, and decreased the proportion of G₀-G₁ and G₂-M phases (P < 0.05). The silencing of PCAT-1 increased the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP, decreased the proportion of S phase in the cell cycle, and enhanced the proportion of G₀-G₁ and G₂-M phase (P < 0.05). Overexpression of PCAT-1 promoted STAT3 protein expression but inhibited PTEN protein expression in HeLa/DDP and SiHa/DDP cells (P < 0.05). The silencing of PCAT-1 inhibited STAT3 protein expression but promoted PTEN protein expression in HeLa/DDP and SiHa/DDP cells (P < 0.05).
Conclusion
PCAT-1 is upregulated in HeLa/DDP and SiHa/DDP cells. PCAT-1 reduces the sensitivity of HeLa/DDP and SiHa/DDP cells to DDP by upregulating the expression of STAT3 and downregulating the expression of PTEN.
- LncRNAs,
- PCAT-1,
- Cervical cancer cells,
- DDP,
- Sensitivity

FullText(HTML)

Competing interests: The authors declare that they have no competing interests.

References (22)

References

[1]	Brisson M, Drolet M. Global elimination of cervical cancer as a public health problem[J]. Lancet Oncol, 2019, 20(3): 319-321. doi: 10.1016/S1470-2045(19)30072-5
[2]	Cohen PA, Jhingran A, Oaknin A, et al. Cervical cancer[J]. Lancet, 2019, 393(10167): 169-182. doi: 10.1016/S0140-6736(18)32470-X
[3]	Zhu H, Luo H, Zhang W, et al. Molecular mechanisms of cisplatin resistance in cervical cancer[J]. Drug Des Devel Ther, 2016, 10: 1885-1895.
[4]	Prensner JR, Iyer MK, Balbin OA, et al. Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression[J]. Nat Biotechnol, 2011, 29(8): 742-749. doi: 10.1038/nbt.1914
[5]	Sur S, Nakanishi H, Steele R, et al. Depletion of PCAT-1 in head and neck cancer cells inhibits tumor growth and induces apoptosis by modulating c-Myc-AKT1-p38 MAPK signalling pathways[J]. BMC Cancer, 2019, 19(1): 354. doi: 10.1186/s12885-019-5562-z
[6]	Ma TT, Zhou LQ, Xia JH, et al. LncRNA PCAT-1 regulates the proliferation, metastasis and invasion of cervical cancer cells[J]. Eur Rev Med Pharmacol Sci, 2018, 22(7): 1907-1913. http://www.europeanreview.org/wp/wp-content/uploads/1907-1913.pdf
[7]	Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm[J]. Cancer Res, 2017, 77(15): 3965-3981. doi: 10.1158/0008-5472.CAN-16-2634
[8]	Li L, Gu M, You B, et al. Long non-coding RNA ROR promotes proliferation, migration and chemoresistance of nasopharyngeal carcinoma[J]. Cancer Sci, 2016, 107(9): 1215-1222. doi: 10.1111/cas.12989
[9]	Bester AC, Lee JD, Chavez A, et al. An integrated genome-wide CRISPRa approach to functionalize lncRNAs in drug resistance[J]. Cell, 2018, 173(3): 649-664. e20. doi: 10.1016/j.cell.2018.03.052
[10]	Fang S, Gao H, Tong Y, et al. Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells[J]. Lab Invest, 2016, 96(1): 60-68. doi: 10.1038/labinvest.2015.123
[11]	Long X, Song K, Hu H, et al. Long non-coding RNA GAS5 inhibits DDP-resistance and tumor progression of epithelial ovarian cancer via GAS5-E2F4-PARP1-MAPK axis[J]. J Exp Clin Cancer Res, 2019, 38(1): 345. doi: 10.1186/s13046-019-1329-2
[12]	Li M, Zhang YY, Shang J, et al. LncRNA SNHG5 promotes cisplatin resistance in gastric cancer via inhibiting cell apoptosis[J]. Eur Rev Med Pharmacol Sci, 2019, 23(10): 4185-4191. http://www.ncbi.nlm.nih.gov/pubmed/31173289
[13]	Wen Q, Liu Y, Lyu H, et al. Long noncoding RNA GAS5, which acts as a tumor suppressor via microRNA 21, regulates cisplatin resistance expression in cervical cancer[J]. Int J Gynecol Cancer, 2017, 27(6): 1096-1108. doi: 10.1097/IGC.0000000000001028
[14]	Feng Y, Zou W, Hu C, et al. Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin[J]. Arch Biochem Biophys, 2017, 623-624: 20-30. doi: 10.1016/j.abb.2017.05.001
[15]	Zhen Q, Gao LN, Wang RF, et al. LncRNA PCAT-1 promotes tumour growth and chemoresistance of oesophageal cancer to cisplatin[J]. Cell Biochem Funct, 2018, 36(1): 27-33. doi: 10.1002/cbf.3314
[16]	Qiao L, Liu X, Tang Y, et al. Knockdown of long non-coding RNA prostate cancer-associated ncRNA transcript 1 inhibits multidrug resistance and c-Myc-dependent aggressiveness in colorectal cancer Caco-2 and HT-29 cells[J]. Mol Cell Biochem, 2018, 441(1-2): 99-108. doi: 10.1007/s11010-017-3177-8
[17]	Shen X, Shen P, Yang Q, et al. Knockdown of long non-coding RNA PCAT-1 inhibits myeloma cell growth and drug resistance via p38 and JNK MAPK pathways[J]. J Cancer, 2019, 10(26): 6502-6510. doi: 10.7150/jca.35098
[18]	Liu K, Ren T, Huang Y, et al. Apatinib promotes autophagy and apoptosis through VEGFR2/STAT3/BCL-2 signaling in osteosarcoma[J]. Cell Death Dis, 2017, 8(8): e3015. doi: 10.1038/cddis.2017.422
[19]	Huang LL, Rao W. SiRNA interfering STAT3 enhances DDP sensitivity in cervical cancer cells[J]. Eur Rev Med Pharmacol Sci, 2018, 22(13): 4098-4106. http://www.europeanreview.org/wp/wp-content/uploads/4098-4106.pdf
[20]	Salmena L. PTEN: History of a tumor suppressor[J]. Methods Mol Biol, 2016, 1388: 3-11. http://www.onacademic.com/detail/journal_1000038443200510_650b.html
[21]	Zuo Q, Liu J, Huang L, et al. AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma[J]. Oncogene, 2018, 37(24): 3275-3289. doi: 10.1038/s41388-018-0205-4
[22]	Du G, Cao D, Meng L. MiR-21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AKT pathway and improves paclitaxel sensitivity in cervical cancer cells[J]. Mol Med Rep, 2017, 15(5): 2713-2719. doi: 10.3892/mmr.2017.6340

[1]	DAI Nan, ZHAO Xiaolong, DAI Xiaoyan, LI Mengxia. Effect of Exosomal APE1 on Sensitivity of NSCLC A549 Cells to Cisplatin[J]. Cancer Research on Prevention and Treatment, 2020, 47(7): 492-497. DOI: 10.3971/j.issn.1000-8578.2020.19.1609
[2]	HUANG Zejian, FANG Chang, YU Baodan, CHENG Qing, LYU Ping. 3E10 Targeting CD24 Enhances Chemotherapy Sensitivity of Hepatocellular Carcinoma HuH-7 Cells[J]. Cancer Research on Prevention and Treatment, 2018, 45(8): 540-544. DOI: 10.3971/j.issn.1000-8578.2018.17.1484
[3]	CAI Rui, CHEN Qiuqiu, JIANG Wei. 5-azacytidine Increases Radiation Sensitivity of Nasopharyngeal Carcinoma Cell Line C666-1[J]. Cancer Research on Prevention and Treatment, 2017, 44(2): 94-97. DOI: 10.3971/j.issn.1000-8578.2017.02.003
[4]	ZHANG Juping, SHI Yehui, JIA Yongsheng, ZHOU Liyan, TONG Zhongsheng. GDF11 is Involved in Human Hepatic Carcinoma Cells SMMC-7721 Proliferation and Sensitivity to DDP[J]. Cancer Research on Prevention and Treatment, 2016, 43(6): 459-462. DOI: 10.3971/j.issn.1000-8578.2016.06.005
[5]	LI Wei, PENG Junqin, LI Jiansheng, TANG Rijie. MR Apparent Diffusion Coefficient Predicts Sensitivity of Nasopharyngeal Carcinoma to Radiotherapy and Related Factors[J]. Cancer Research on Prevention and Treatment, 2015, 42(12): 1221-1226. DOI: 10.3971/j.issn.1000-8578.2015.12.011
[6]	HU Lili, YIN Yanjun, ZHONG Wenjuan, QIU Feng. miR-200c Enhances Sensitivity of Lung Cancer Cell A549 to Paclitaxel and Gefitinib and Related Mechanism[J]. Cancer Research on Prevention and Treatment, 2015, 42(08): 760-764. DOI: 10.3971/j.issn.1000-8578.2015.08.003
[7]	CAO Xinmei, ZHANG Daiquan, XIA Jiyi, WANG Xu, GAO Yan, XIONG Wei. Effects of HER2 shRNA on Chemotherapy Sensitivity of Mouse Lewis Cells[J]. Cancer Research on Prevention and Treatment, 2014, 41(05): 366-368. DOI: 10.3971/j.issn.1000-8578.2014.05.004
[8]	Yang Qingshan, Liu Yuanyuan, Jiang Lipeng. Effect of Expression Vector of Human BAG-1 Gene on Radio-sensitivity of Lung Adenocarcinoma Cells[J]. Cancer Research on Prevention and Treatment, 2012, 39(02): 127-129. DOI: 10.3971/j.issn.1000-8578.2012.02.002
[9]	FANG Chuan, TAN Yan-li, WANG Jia-liang, SHI Yan-fang, SHAN Xiao-song, LI Wei. Primary Culture and Drug Sensitivity of Human Glioma Cells[J]. Cancer Research on Prevention and Treatment, 2010, 37(12): 1380-1382. DOI: 10.3971/j.issn.1000-8578.2010.12.012
[10]	ZHANG Wei, GU Min. Geldanamycin Sensitizes Human Breast Cancer Cells to Adriamycin both in vitro and in vivo[J]. Cancer Research on Prevention and Treatment, 2010, 37(10): 1109-1112. DOI: 10.3971/j.issn.1000-8578.2010.10.004

Cited By

Cited by

Periodical cited type(2)

1.	周青青，吴捷，李节繁. lncRNA PCAT-1通过调控HMGB1诱导的肝细胞焦亡在急性肝损伤中的作用机制研究. 健康研究. 2025(01): 79-83+121 .
2.	魏丽，陈玉忠，杜军，李艳，张慧慧，李多杰. LncRNA LUCAT1促进宫颈癌SiHa细胞的增殖、转移及顺铂耐药. 包头医学院学报. 2023(05): 22-28 .

Other cited types(0)

Figures(6)

Get Citation

PDF

XML

Article views (1203) PDF downloads (255) Cited by(2)

Turn off MathJax

Article Contents

Abstract

References

LncRNA PCAT-1 Reduces Sensitivity of Cervical Carcinoma Cells to Cisplatin by Regulating STAT3 and PTEN Expression