https://doi.org/10.4081/ejh.2023.3653

Knockdown of ARHGAP30 inhibits ovarian cancer cell proliferation, migration, and invasiveness by suppressing the PI3K/AKT/mTOR signaling pathway

Vol. 67 No. 2 (2023)
Submitted: 21 January 2023
Accepted: 22 April 2023
Published: 11 May 2023
ARHGAP30, ovarian cancer, cell invasiveness, PI3K/AKT/mTOR pathway
Abstract Views: 400
PDF: 265
HTML: 14
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Xiaoyan Chu
https://orcid.org/0009-0000-7258-6176
College of Medicine, Nanchang University, Nanchang; Department of Gynecological Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Jun Lou
Department of Gynecological Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Yun Yi
Department of Gynecological Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Linlin Zhong
Department of Gynecological Oncology, Jiangxi Cancer Hospital, Nanchang, Jiangxi, China.
Ouping Huang
xiaoli0775@126.com
College of Medicine, Nanchang University, Nanchang; Key Laboratory of Women’s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi, China.

The mortality and morbidity rates of ovarian cancer (OC) are high, but the underlying mechanisms of OC have not been characterized. In this study, we determined the role of Rho GTPase Activating Protein 30 (ARHGAP30) in OC progression. We measured ARHGAP30 abundance in OC tissue samples and cells using immunohistochemistry (IHC) and RT-qPCR. EdU, transwell, and annexin V/PI apoptosis assays were used to evaluate proliferation, invasiveness, and apoptosis of OC cells, respectively. The results showed that ARHGAP30 was overexpressed in OC tissue samples and cells. Inhibition of ARHGAP30 suppressed growth and metastasis of OC cells, and enhanced apoptosis. Knockdown of ARHGAP30 in OC cells significantly inhibited the PI3K/AKT/mTOR pathway. Treatment with the PI3K/AKT/mTOR pathway inhibitor buparlisib simulated the effects of ARHGAP30 knockdown on growth, invasiveness, and apoptosis of OC cells. Following buparlisib treatment, the expression levels of p-PI3K, p-AKT, and p-mTOR were significantly decreased. Furthermore, buparlisib inhibited the effects of ARHGAP30 upregulation on OC cell growth and invasiveness. In conclusion, ARHGAP30 regulated the PI3K/AKT/mTOR pathway to promote progression of OC.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Liu S, Chen X, Huang K, Xiong X, Shi Y, Wang X, et al. Long noncoding RNA RFPL1S-202 inhibits ovarian cancer progression by downregulating the IFN-beta/STAT1 signaling. Exp Cell Res 2023;422:113438. DOI: https://doi.org/10.1016/j.yexcr.2022.113438
Li H, Jiang F, Du Y, Li N, Chen Z, Cai H, et al. Identification of differential DNA methylation alterations of ovarian cancer in peripheral whole blood based on within-sample relative methylation orderings. Epigenetics 2022;17:314-326. DOI: https://doi.org/10.1080/15592294.2021.1900029
Luo HJ, Hu ZD, Cui M, Zhang XF, Tian WY, Ma CQ, et al. Diagnostic performance of CA125, HE4, ROMA, and CPH-I in identifying primary ovarian cancer. J Obstet Gynaecol Res 2023;49:998-1006. DOI: https://doi.org/10.1111/jog.15540
Wong DCP, Pan CQ, Er SY, Thivakar T, Rachel TZY, Seah SH, et al. The scaffold RhoGAP protein ARHGAP8/ BPGAP1 synchronizes Rac and Rho signaling to facilitate cell migration. Mol Biol Cell 2023;34:ar13. DOI: https://doi.org/10.1091/mbc.E21-03-0099
Yi M, Zhang D, Song B, Zhao B, Niu M, Wu Y, et al. Increased expression of ECT2 predicts the poor prognosis of breast cancer patients. Exp Hematol Oncol 2022;11:107. DOI: https://doi.org/10.1186/s40164-022-00361-3
Wang T, Rao D, Yu C, Sheng J, Luo Y, Xia L, et al. RHO GTPase family in hepatocellular carcinoma. Exp Hematol Oncol 2022;11:91. DOI: https://doi.org/10.1186/s40164-022-00344-4
Liu H, Huang J, Zhang X, Liu G, Liang W, Zhu G, et al. The RAC/ROP GTPase activator OsRopGEF10 functions in crown root development by regulating cytokinin signaling in rice. Plant Cell 2023;35:453-68. DOI: https://doi.org/10.1093/plcell/koac297
Hu S, Zhang W, Ye J, Zhang Y, Zhang D, Peng J, et al. DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival. Aging (Albany NY) 2021;13:25799-845. DOI: https://doi.org/10.18632/aging.203762
Wang J, Qian J, Hu Y, Kong X, Chen H, Shi Q, et al. ArhGAP30 promotes p53 acetylation and function in colorectal cancer. Nat Commun 2014;5:4735. DOI: https://doi.org/10.1038/ncomms5735
Mao X, Tong J. ARHGAP30 suppressed lung cancer cell proliferation, migration, and invasion through inhibition of the Wnt/beta-catenin signaling pathway. Onco Targets Ther 2018;11:7447-57. DOI: https://doi.org/10.2147/OTT.S175255
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res 2017;45:W98-W102. DOI: https://doi.org/10.1093/nar/gkx247
von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, et al. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res 2005;33:D433-437. DOI: https://doi.org/10.1093/nar/gki005
Zhang M, Yue H, Huang X, Wang J, Li Z, Deng X. Novel platinum nanoclusters activate PI3K/AKT/mTOR signaling pathway-mediated autophagy for cisplatin-resistant ovarian cancer therapy. ACS Appl Mater Interfaces 2022;14:48502-14. DOI: https://doi.org/10.1021/acsami.2c15143
Zi D, Li Q, Xu CX, Zhou ZW, Song GB, Hu CB, et al. CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma. Aging (Albany NY) 2022;14:4673-98. DOI: https://doi.org/10.18632/aging.203241
Ghoneum A, Gonzalez D, Afify H, Shu J, Hegarty A, Adisa J, et al. Compound C inhibits ovarian cancer progression via PI3K-AKT-mTOR-NFkappaB pathway. Cancers (Basel) 2022;14:5099. DOI: https://doi.org/10.3390/cancers14205099
Xie W, Yu J, Yin Y, Zhang X, Zheng X, Wang X. OCT4 induces EMT and promotes ovarian cancer progression by regulating the PI3K/AKT/mTOR pathway. Front Oncol 2022;12:876257. DOI: https://doi.org/10.3389/fonc.2022.876257
Li H, Zeng J, Shen K. PI3K/AKT/mTOR signaling pathway as a therapeutic target for ovarian cancer. Arch Gynecol Obstet 2014;290:1067-78. DOI: https://doi.org/10.1007/s00404-014-3377-3
Li CX, Men CD, Yang WH, Chen R, Zhu JH, Cheng ZP. Repressing IRS1/2 by NT157 inhibits the malignant behaviors of ovarian cancer through inactivating PI3K/AKT/mTOR pathway and inducing autophagy. Kaohsiung J Med Sci 2023;39:377-89. DOI: https://doi.org/10.1002/kjm2.12652
Li M, Zhang W, Wang Y, Huang K, Sun T, Qiu Z, et al. DDTC suppresses ovarian cancer development via the PI3K/AKT/mTOR signaling pathway. Dis Markers 2022;2022:1941077. DOI: https://doi.org/10.1155/2022/1941077
Weng H, Feng X, Lan Y, Zheng Z. TCP1 regulates PI3K/AKT/mTOR signaling pathway to promote proliferation of ovarian cancer cells. J Ovarian Res 2021;14:82. DOI: https://doi.org/10.1186/s13048-021-00832-x
Bi X, Lv X, Liu D, Guo H, Yao G, Wang L, et al. METTL3-mediated maturation of miR-126-5p promotes ovarian cancer progression via PTEN-mediated PI3K/Akt/mTOR pathway. Cancer Gene Ther 2021;28:335-49. DOI: https://doi.org/10.1038/s41417-020-00222-3
Wu A, Lin L, Li X, Xu Q, Xu W, Zhu X, et al. Overexpression of ARHGAP30 suppresses growth of cervical cancer cells by downregulating ribosome biogenesis. Cancer Sci 2021;112:4515-25. DOI: https://doi.org/10.1111/cas.15130
Yagi H, Onoyama I, Asanoma K, Kawakami M, Maenohara S, Kodama K, et al. Tumor-derived ARHGAP35 mutations enhance the Galpha(13)-Rho signaling axis in human endometrial cancer. Cancer Gene Ther 2022;30:313-23. DOI: https://doi.org/10.1038/s41417-022-00547-1
Naji L, Pacholsky D, Aspenstrom P. ARHGAP30 is a Wrch-1-interacting protein involved in actin dynamics and cell adhesion. Biochem Biophys Res Commun 2011;409:96-102. DOI: https://doi.org/10.1016/j.bbrc.2011.04.116
Zhou Y, Hua Z, Zhu Y, Wang L, Chen F, Shan T, et al. Upregulation of ARHGAP30 attenuates pancreatic cancer progression by inactivating the beta-catenin pathway. Cancer Cell Int 2020;20:225. DOI: https://doi.org/10.1186/s12935-020-01288-7
Tian T, Li X, Zhang J. mTOR signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int J Mol Sci 2019;20:755. DOI: https://doi.org/10.3390/ijms20030755
Xu W, Yang Z, Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adh Migr 2015;9:317-24. DOI: https://doi.org/10.1080/19336918.2015.1016686
Wang Y, Luo X, Wu N, Liao Q, Wang J. SRC-3/TRAF4 facilitates ovarian cancer development by activating the PI3K/AKT signaling pathway. Med Oncol 2023;40:76. DOI: https://doi.org/10.1007/s12032-022-01944-0

Ethics Approval

The current study was approved by the Medical Ethics Committee of Jiangxi Cancer Hospital (no. 2022.023, date 2022.10.10)

How to Cite

Chu, X., Lou, J., Yi, Y., Zhong, L., & Huang, O. (2023). Knockdown of ARHGAP30 inhibits ovarian cancer cell proliferation, migration, and invasiveness by suppressing the PI3K/AKT/mTOR signaling pathway. European Journal of Histochemistry, 67(2). https://doi.org/10.4081/ejh.2023.3653
Copyright (c) 2023 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.