Effect of Yes-associated proteins on biological behaviors of human cervical cancer SiHa cells

Fang ZHAO, Zhenling LI, Lihua PIAO, Longzhe HAN, Yinji CUI, Chunji QUAN, Xuemei JIN

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J Jilin Univ Med Ed ›› 2025, Vol. 51 ›› Issue (1) : 68-75. DOI: 10.13481/j.1671-587X.20250109
Research in basic medicine

Effect of Yes-associated proteins on biological behaviors of human cervical cancer SiHa cells

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Abstract

Objective To discuss the effect of Yes-associated protein （YAP） silencing on the proliferation， migration， and invasion capabilities of the human cervical cancer （CC） SiHa cells. Methods The human CC SiHa cells were cultured in vitro， and the lentiviral YAP shRNA was transfected into the SiHa cells to establish stably transfected YAP-shRNA experimental group （sh-YAP group） and empty plasmid control group （control group）. Western blotting method was used to detect the silencing effect of YAP； immunofluorescence method was used to detect the microfilament number and morphology of actin filaments （F-actin） in the cells in both groups； CCK-8 method was used to detect the survival rates of the cells in two groups； Transwell chamber assay and wound healing assay were used to detect the numbers of migration and invasion cells and scratch healing rates of the cells in two groups； Western blotting method was used to detect the expression levels of epithelial-mesenchymal transition （EMT） markers （E-cadherin and Snail）， DNA damage repair-related proteins （γ-H2AX）， and apoptosis-related proteins ［c-MYC and B-cell lymphoma-2 （Bcl-2）］ in the cells in two groups. Results The results of lentiviral YAP shRNA transfection into SiHa cells showed that the expression level of YAP protein in the SiHa cells was significantly decreased （P<0.05）. The immunofluorescence results showed that after YAP silencing， the F-actin in SiHa cells was sparse and regularly arranged， with a reduced number of cells and a shriveled appearance. The CCK-8 results showed that compared with control group， the survival rate of the SiHa cells in sh-YAP group was significantly decreased cultured for 24 and 48 h （P<0.01）. The results of Transwell chamber assay and the wound healing assay showed that compared with control group， the numbers of migration and invasion SiHa cells in sh-YAP group were significantly decreased （P<0.01）， and the cell scratch healing rates were signifiantly decreased（P<0.05）. The Western blotting results showed that compared with control group， the expression level of E-cadherin protein in the cells in sh-YAP group was increased （P<0.05）， and the expression levels of c-MYC， Bcl-2， and γ-H2AX proteins were decreased （P<0.05 or P<0.01）. Conclusion YAP gene silencing leads to the depolymerization of F-actin in the human CC SiHa cells and regulates the apoptosis and DNA damage repair， potentially reversing the EMT process， thereby inhibiting the proliferation and migration of the tumor cells.

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Cervical neoplasm / Yes-associated protein / Cell proliferation / Cell migration

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Fang ZHAO , Zhenling LI , Lihua PIAO , et al . Effect of Yes-associated proteins on biological behaviors of human cervical cancer SiHa cells. Journal of Jilin University(Medicine Edition). 2025, 51(1): 68-75 https://doi.org/10.13481/j.1671-587X.20250109

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis
1
SUNG H， FERLAY 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.
本文引用 [1]
2
RODEN R B S， STERN P L. Opportunities and challenges for human papillomavirus vaccination in cancer［J］. Nat Rev Cancer， 2018， 18（4）： 240-254.
本文引用 [1]
3
MAEHAMA T， NISHIO M， OTANI J， et al. The role of Hippo-YAP signaling in squamous cell carcinomas［J］. Cancer Sci， 2021， 112（1）： 51-60.
本文引用 [2]
4
LI H L， LI Q Y， JIN M J， et al. A review： Hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression［J］. J Cancer Res Clin Oncol， 2021， 147（6）： 1569-1585.
本文引用 [2]
5
李嫣晓， 陈红霞， 程梦蝶， 等. 铁死亡与心肌纤维化相关信号通路的研究进展［J］. 郑州大学学报（医学版），2024， 59（2）： 195-201.
本文引用 [1]
6
于 晓， 成慧君， 田淑贞， 等. 多模态成像技术引导下组织间徒手插植近距离放射治疗宫颈癌的效果及剂量学分析［J］. 郑州大学学报（医学版）， 2024， 59（2）： 191-195.
本文引用 [1]
7
赵亚南， 阿地拉·艾皮热， 李金耀. CRISPR/Cas9技术在宫颈癌治疗中的应用进展［J］. 国际生物医学工程杂志， 2023， 46（2）： 144-150.
本文引用 [1]
8
YADAV C， YADAV R， CHABBRA R， et al. Overview of genetic and epigenetic regulation of human papillomavirus and apoptosis in cervical cancer［J］. Apoptosis， 2023， 28（5/6）： 683-701.
本文引用 [1]
9
MA S H， MENG Z P， CHEN R， et al. The hippo pathway： biology and pathophysiology［J］. Annu Rev Biochem， 2019， 88： 577-604.
本文引用 [2]
10
HUANG Z S， ZHOU J， LEUNG W T， et al. The novel role of hippo-YAP/TAZ in immunity at the mammalian maternal-fetal interface： opportunities， challenges［J］. Biomed Pharmacother， 2020， 126： 110061.
本文引用 [1]
11
LING H H， KUO C C， LIN B X， et al. Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer［J］. Exp Cell Res， 2017， 350（1）： 218-225.
本文引用 [2]
12
XIAO W F， WANG J Y， OU C， et al. Mutual interaction between YAP and c-Myc is critical for carcinogenesis in liver cancer［J］. Biochem Biophys Res Commun， 2013， 439（2）： 167-172.
本文引用 [2]
13
DEY A， VARELAS X， GUAN K L. Targeting the Hippo pathway in cancer， fibrosis， wound healing and regenerative medicine［J］. Nat Rev Drug Discov， 2020， 19（7）： 480-494.
本文引用 [1]
14
SONG J， GAO Q L， WU B W， et al. Discovery of tertiary amide derivatives incorporating benzothiazole moiety as anti-gastric cancer agents in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway［J］. Eur J Med Chem， 2020， 203： 112618.
本文引用 [1]
15
LEHTIMÄKI J， HAKALA M， LAPPALAINEN P. Actin filament structures in migrating cells［J］. Handb Exp Pharmacol， 2017， 235： 123-152.
本文引用 [1]
16
PENG J M， BERA R， CHIOU C Y， et al. Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice［J］. Hepatology， 2018， 67（6）： 2226-2243.
本文引用 [1]
17
ZHANG J L， ZHOU Y H， TANG P M K， et al. Mechanotransduction and cytoskeleton remodeling shaping YAP1 in gastric tumorigenesis［J］. Int J Mol Sci， 2019， 20（7）： 1576.
本文引用 [1]
18
QIU B J， WEI W， ZHU J W， et al. EMT induced by loss of LKB1 promotes migration and invasion of liver cancer cells through ZEB1-induced YAP signaling［J］. Oncol Lett， 2018， 16（5）： 6465-6471.
本文引用 [1]
19
PENG Y R， HU S S， ZHANG K， et al. Downregulation of microRNA-130a inhibits oral squamous cell carcinoma proliferation and metastasis via the hippo-YAP pathway［J］. Cancer Manag Res， 2021， 13： 4829-4840.
20
SHAO D D， XUE W， KRALL E B， et al. KRAS and YAP1 converge to regulate EMT and tumor survival［J］. Cell， 2014， 158（1）： 171-184.
21
XIONG Y J， DONG L R， BAI Y， et al. Piezo1 activation facilitates ovarian cancer metastasis via Hippo/YAP signaling axis［J］. Channels， 2022， 16（1）： 159-166.
本文引用 [1]
22
HE L L， YUAN L， YU W T， et al. A regulation loop between YAP and NR4A1 balances cell proliferation and apoptosis［J］. Cell Rep， 2020， 33（3）： 108284.
本文引用 [1]
23
HSIEH A L， DANG C V. MYC， metabolic synthetic lethality， and cancer［J］. Recent Results Cancer Res， 2016， 207： 73-91.
本文引用 [1]
24
CHEN Y L， HAN L， BAI L P， et al. Trichosanthin inhibits the proliferation of cervical cancer cells and downregulates STAT-5/C-myc signaling pathway［J］. Pathol Res Pract， 2019， 215（4）： 632-638.
本文引用 [1]
25
TURATO C， CANNITO S， SIMONATO D， et al. SerpinB3 and Yap interplay increases myc oncogenic activity［J］. Sci Rep， 2015， 5： 17701.
本文引用 [1]
26
SONG Y， FU J， ZHOU M， et al. Activated Hippo/Yes-associated protein pathway promotes cell proliferation and anti-apoptosis in endometrial stromal cells of endometriosis［J］. J Clin Endocrinol Metab， 2016， 101（4）： 1552-1561.
本文引用 [1]
27
ZHANG Y， WANG Y， ZHOU D， et al. Radiation-induced YAP activation confers glioma radioresistance via promoting FGF2 transcription and DNA damage repair［J］. Oncogene， 2021， 40（27）： 4580-4591.
本文引用 [1]
28
KUO L J， YANG L X. Gamma-H2AX-a novel biomarker for DNA double-strand breaks［J］. In Vivo， 2008， 22（3）： 305-309.
本文引用 [1]
29
SHARMA A， SINGH K， ALMASAN A. Histone H2AX phosphorylation： a marker for DNA damage［J］. Methods Mol Biol， 2012， 920： 613-626.
本文引用 [1]
30
SAHA S T， RUNDLE S， KOTSOPOULOS I C， et al. Determining the potential of DNA damage response （DDR） inhibitors in cervical cancer therapy［J］. Cancers （Basel）， 2022， 14（17）： 4288.
本文引用 [1]

赵芳参与细胞培养实验和论文撰写，李珍玲参与细胞功能实验和数据分析，朴丽花参与实验指导，韩龙哲和崔银姬参与文献检索及数据整理，权春姬参与论文的统计学分析和课题指导，金雪梅参与论文的整体设计和论文修改。

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