Screening and Validation of Potential Prognostic Markers of Cervical Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database

Yijun YAN; Hongying YANG; Hongping ZHANG; Zheng LI; Yue JIA; Min ZHAO

doi:10.12259/j.issn.2095-610X.S20230808

Volume 44 Issue 8

Aug. 2023

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Yijun YAN, Hongying YANG, Hongping ZHANG, Zheng LI, Yue JIA, Min ZHAO. Screening and Validation of Potential Prognostic Markers of Cervical Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database[J]. Journal of Kunming Medical University, 2023, 44(8): 14-26. doi: 10.12259/j.issn.2095-610X.S20230808

Citation:

Yijun YAN, Hongying YANG, Hongping ZHANG, Zheng LI, Yue JIA, Min ZHAO. Screening and Validation of Potential Prognostic Markers of Cervical Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database[J]. Journal of Kunming Medical University, 2023, 44(8): 14-26. doi: 10.12259/j.issn.2095-610X.S20230808

Citation:

Yijun YAN, Hongying YANG, Hongping ZHANG, Zheng LI, Yue JIA, Min ZHAO. Screening and Validation of Potential Prognostic Markers of Cervical Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database[J]. Journal of Kunming Medical University, 2023, 44(8): 14-26. doi: 10.12259/j.issn.2095-610X.S20230808

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Screening and Validation of Potential Prognostic Markers of Cervical Squamous Cell Carcinoma Based on The Cancer Genome Atlas Database

doi: 10.12259/j.issn.2095-610X.S20230808

1.
Dept. of Nuclear Medicine，Affiliated Hospital of Yunnan University，Kunming Yunnan 650021
2.
Dept. of Gynecology
3.
Dept. of Medical Administration，The Third Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650118，China

Received Date: 2023-05-17
Available Online: 2023-09-01
Publish Date: 2023-08-30

Abstract

Abstract

Objective To screen and verify the potential prognostic markers of miRNA in cervical squamous cell carcinoma （CESC）, and to explore the molecular mechanism of CESC. Methods Using miRNA sequencing data of cervical squamous cell carcinoma tissues and adjacent tissues in the TCGA database, as well as patient clinical data, a risk model for predicting the prognosis of cervical squamous cell carcinoma patients was constructed using bioinformatics analysis. The model consists of four miRNAs （miR-505-5p, miR-142-3p, miR-532-5p, miR-218-1-3p）. The diagnostic performance of the model was evaluated. Reverse transcription-polymerase chain reaction （RT-PCR） was used to detect the expression levels of these four miRNAs in 21 pairs of cervical squamous cell carcinoma tissues and adjacent normal tissues. MiR-505-5p, which showed significant differential expression, was selected for further analysis to examine its relationship with various clinical pathological features of cervical squamous cell carcinoma patients. Transfection of miR-505-5p mimics into cervical squamous cell carcinoma cells was performed to investigate the impact of miR-505-5p on the cellular functions of cervical squamous cell carcinoma. Finally, potential target genes of miR-505-5p were predicted using bioinformatics methods and validated through RT-PCR and Western blot experiments. Results By analyzing the cervical squamous cell carcinoma （CESC） related data from the TCGA database, a prognostic risk model composed of 4 miRNAs （miR-505-5p, miR-142-3p, miR-532-5p, miR-218-1-3p） was constructed. The prognostic risk model effectively stratifies CESC patients into high-risk and low-risk groups for adverse prognosis. The expression of miR-505-5p in the collected 21 pairs of CESC tissues was lower than that in adjacent tissues （P < 0.05）, and its expression level was negatively correlated with the clinical stage and invasion degree of CESC patients. Overexpression of miR-505-5p inhibited the proliferation （P < 0.05） and migration of cervical squamous cell carcinoma SiHa cells, and promoted apoptosis （P < 0.05）. TBL1XR1 was identified as the best predicted target gene of miR-505-5p, and overexpression of miR-505-5p decreased the RNA and protein levels of TBL1XR1 （P < 0.05）. Conclusion miR-505-5p can be used as a potential prognostic marker in patients with CESC, and miR-505-5p may play a tumor suppressive role in CESC by targeting TBL1XR1.
- Cervical squamous cell carcinoma,
- Prognostic markers,
- miR-505-5p,
- TBL1XR1

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References(22)

References

[1]	Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2018,68(6):394-424. doi: 10.3322/caac.21492
[2]	Yang M,Du J,Lu H,et al. Global trends and age-specific incidence and mortality of cervical cancer from 1990 to 2019: an international comparative study based on the Global Burden of Disease[J]. BMJ Open,2022,12(7):e055470. doi: 10.1136/bmjopen-2021-055470
[3]	FENG C,DONG J,CHANG W,et al. The progress of methylation regulation in gene expression of cervical cancer[J]. Int J Genomics,2018,2018:8260652. doi: 10.1155/2018/8260652
[4]	LV X J,TANG Q,TU Y Q,et al. Long noncoding RNA PCAT6 regulates cell growth and metastasis via Wnt/β-catenin pathway and is a prognosis marker in cervical cancer[J]. Eur Rev Med Pharmacol Sci,2019,23(5):1947-1956.
[5]	Sung H,Feriay J,Siegel R L,et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin,2021,71(3):209-249.
[6]	Xie M,Nie F Q,Sun M,et al. Decreased long noncoding RNA SPRY4-IT1 contributing to gastric cancer cell metastasis partly via affecting epithelialmesenchymal transition[J]. J Transl Med,2015,13:250. doi: 10.1186/s12967-015-0595-9
[7]	WangY,Luo J,Zhang H,et al. microRNAs in the same clusters evolve to coordinately regulate functionally related genes[J]. Mol Biol Evol,2016,33(9):2232-2247. doi: 10.1093/molbev/msw089
[8]	Shen J,Hung M C. Signaling-mediated regulation of MicroRNA processing[J]. Cancer Res,2015,75(5):783-791. doi: 10.1158/0008-5472.CAN-14-2568
[9]	Svoronos A A,Engelman D M,Slack F J. OncomiR or tumor suppressor? The duplicity of microRNAs in cancer[J]. Cancer Res,2016,76(13):3666-3670. doi: 10.1158/0008-5472.CAN-16-0359
[10]	Tornesello M L,Faraonio R,Buonaguro L T,et al. The Role of microRNAs,Long Non-coding RNAs,and Circular RNAs in Cervical Cancer[J]. Front Oncol,2020,10:150. doi: 10.3389/fonc.2020.00150
[11]	张勇,张哲,朱育焱等. miR-505-5p在膀胱癌细胞中靶向调控PLK1抑制细胞增殖和迁移[J]. 实用肿瘤杂志,2019,34(5):402-409. doi: 10.13267/j.cnki.syzlzz.2019.05.004 ZHANG Y,ZHANG Z,ZHU Y Y,et al. miR-505-5p inhibits proliferation and migration of human bladder cancer cells by regulating PLK1[J]. Journal of Practical Oncology,2019,34(5):402-409. doi: 10.13267/j.cnki.syzlzz.2019.05.004
[12]	Qin Z,He W,Tang J,et al. MicroRNAs provide feedback regulation of epithelial-mesenchymal transition induced by growth factors[J]. J Cell Physiol,2016,231(1):120-129. doi: 10.1002/jcp.25060
[13]	Perissi V,Scafoglio C,Zhang J,et al. TBL1 and TBLR1 phosphorylation on regulated gene promoters overcomes dual CtBP and NCoR/SMRT transcriptional repression checkpoints[J]. Mol Cell,2008,29(6):755-766. doi: 10.1016/j.molcel.2008.01.020
[14]	Xi X,Wu Q,Bao Y,et al. Overexpression of TBL1XR1 confers tumorigenic capability and promotes recurrence of osteosarcoma[J]. Eur J Pharmacol,2019,844:259-267. doi: 10.1016/j.ejphar.2018.12.013
[15]	Pan Q,Shao Z G,Zhang Y J,et al. MicroRNA-1178-3p suppresses the growth of hepatocellular carcinoma by regulating transducin (beta)-like 1 X-linked receptor 1[J]. Hum Cell,2021,34(5):1466-1477. doi: 10.1007/s13577-021-00565-5
[16]	Lai W Q, Yue Y H, Zeng GH. MicroRNA-34c-5p Reduces Malignant Properties of Lung Cancer Cells through Regulation of TBL1XR1/Wnt/β-catenin Signaling. CURRENT MOLECULAR MEDICINE. 2023. doi: 10.2174/1566524023666230330083819.
[17]	Venturutti L,Teater M,Zhai A,et al. TBL1XR1 mutations drive extranodal lymphoma by inducing a pro-tumorigenic memory fate[J]. Cell,2020,182(2):297-316. doi: 10.1016/j.cell.2020.05.049
[18]	张银鹏,孙金兵,宗洋等. 干扰TBL1XR1表达调控c -Met /PI3K/Akt通路对胰腺癌细胞生物学行为影响的实验研究[J]. 临床肿瘤学杂志,2021,26(2):97-103.
[19]	Zhang T,Liu C,Yu Y,et al. TBL1XR1 is involved in c-Met-medi- ated tumorigenesis of human nonsmall cell lung cancer[J]. Cancer Gene Ther,2020,27:136-146. doi: 10.1038/s41417-019-0111-0
[20]	Lu J,Bang H J,Su S M,et al. Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 signaling[J]. Oncogene,2020,40(5):922-936.
[21]	Wang X F,Xu X Y,Cai W Z,et al. TBL1XR1 mutation predicts poor outcome in primary testicular diffuse large B-cell lymphoma patients[J]. Biomark Res,2020,8:10. doi: 10.1186/s40364-020-00189-1
[22]	Wang J,Ou J,Guo Y,et al. TBLR1 is a novel prognostic marker and promotes epithelial-mesenchymal transition in cervical cancer[J]. Br J Cancer,2014,111(1):112-124. doi: 10.1038/bjc.2014.278

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