KRT17 enhances carboplatin resistance in ovarian cancer through the AKT/mTOR pathway
1Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, 210006 Nanjing, Jiangsu, China
DOI: 10.22514/ejgo.2022.032 Vol.43,Issue 4,August 2022 pp.49-57
Submitted: 13 May 2022 Accepted: 30 June 2022
Published: 15 August 2022
Ovarian cancer has gradually evolved into a killer of women’s health. Keratin 17 (KRT17) belongs to keratin family. The role of KRT17 in ovarian cancer is not yet clear. Carboplatin-resistant cell lines of ovarian cancer were established, and the effect of carboplatin on the cell viability of SKOV3-CBP, A2780-CBP (carboplatin-resistant cell lines) and SKOV3, A2780 cells were investigated by MTT assay; the expression of KRT17 was predicted and verified by Gene Expression Profiling Interactive Analysis (GEPIA) and western blot (WB) to compare ovarian cancer and normal tissues; KRT17 was successfully knocked down in carboplatin-resistant cell lines, the effect of carboplatin on the cell viability of carboplatin-resistant cell lines and non-drug-resistant cell lines was studied by MTT assay, combined with colony formation assay to study the effect of knockdown of KRT17 on cell clonality; flow cytometry and WB to study the effect of knockdown of KRT17 on cell cycle and apoptosis, and targeted signaling pathway. The results showed that as for the expression of KRT17, compared to normal tissues, ovarian cancer was higher than that; SKOV3-CBP and A2780-CBP were not highly sensitive to drugs and had strong drug resistance. After knocking down KRT17, the drug resistance decreased, the cell cycle was arrested in G0/G1, the protein expression levels of Cyclin D1 and cyclin dependent kinase 4 (CDK4) decreased, the apoptosis level increased and the protein expression level increased; KRT17 mainly plays a regulatory role by targeting AKT/mammalian (or mechanistic) target of rapamycin (AKT/mTOR). This study found that KRT17 could increase the carboplatin resistance of ovarian cancer cells by regulating the AKT/mTOR pathway, promoting the cycle process of ovarian cancer cells, and inhibit apoptosis.
Ovarian cancer; AKT/mTOR; Carboplatin; Drug resistance
Cuixia Yu,Qian Yu,Jing Lu,Jie Zhou. KRT17 enhances carboplatin resistance in ovarian cancer through the AKT/mTOR pathway. European Journal of Gynaecological Oncology. 2022. 43(4);49-57.
 Arndt T, Taube ET, Deubzer HE, Rothe K, Calaminus G, Sehouli J, et al. Management of malignant dysgerminoma of the ovary. European Journal of Gynaecological Oncology. 2022; 43: 353–362.
 Kaser EC, Lequio M, Zhu Z, Hunzeker ZE, Heslin AJ, D’mello KP, et al. Ovarian cancer immunotherapy en route: IL9 inhibits growth of ovarian cancer and upregulates its expression of Ox40L and 4-1BBL. European Journal of Gynaecological Oncology. 2022; 43: 163–168.
 Zhou J, Jiang Y, Chen H, Wu Y, Zhang L. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway. Cell Proliferation. 2020; 53: e12739.
 Jiang X, Cheng Y, He Y, Cong S, Sun L, Wu D, et al. LNC00115 mediates cisplatin resistance by regulating the miR-7/ERK signalling pathway in ovarian cancer. Cancer Management and Research. 2021; 13: 3817–3826.
 Wang Z, Yang MQ, Lei L, Fei LR, Zheng YW, Huang WJ, et al. Overexpression of KRT17 promotes proliferation and invasion of non-small cell lung cancer and indicates poor prognosis. Cancer Management and Research. 2019; 11: 7485–7497.
 Li D, Ni XF, Tang H, Zhang J, Zheng C, Lin J, et al. KRT17 functions as a tumor promoter and regulates proliferation, migration and invasion in pancreatic cancer via mTOR/S6k1 pathway. Cancer Management and Research. 2020; 12: 2087–2095.
 Li J, Chen Q, Deng Z, Chen X, Liu H, Tao Y, et al. KRT17 confers paclitaxel-induced resistance and migration to cervical cancer cells. Life Sciences. 2019; 224: 255–262.
 Li C, Su H, Ruan C, Li X. Keratin 17 knockdown suppressed malignancy and cisplatin tolerance of bladder cancer cells, as well as the activation of AKT and ERK pathway. Folia Histochemica et Cytobiologica. 2021; 59: 40–48.
 Lu Z, Yang H, Cao H, Huo C, Chen Y, Liu D, et al. Forsythoside a protects against lipopolysaccharide-induced acute lung injury through up-regulating microRNA-124. Clinical Science. 2020; 134: 2549–2563.
 Wang Y, Lang H, Yuan J, Wang J, Wang R, Zhang X, et al. Overexpression of keratin 17 is associated with poor prognosis in epithelial ovarian cancer. Tumor Biology. 2013; 34: 1685–1689.
 Ujiie D, Okayama H, Saito K, Ashizawa M, Thar Min AK, Endo E, et al. KRT17 as a prognostic biomarker for stage II colorectal cancer. Carcinogenesis. 2020; 41: 591–599.
 McGuire S. World cancer report 2014. Geneva, Switzerland: world health organization, international agency for research on cancer, who press, 2015. Advances in Nutrition. 2016; 7: 418–419.
 Menon U, Karpinskyj C, Gentry-Maharaj A. Ovarian cancer prevention and screening. Obstetrics & Gynecology. 2018; 131: 909–927.
 Camilloni A, Nati G, Maggiolini P, Romanelli A, Carbone G, Giannarelli D, et al. Chronic non-cancer pain in primary care: an Italian cross-sectional study. Signa Vitae. 2021; 17: 54–62.
 Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ. Hereditary cancer syndromes—a primer on diagnosis and management. Mayo Clinic Proceedings. 2019; 94: 1084–1098.
 Moschetta M, George A, Kaye SB, Banerjee S. BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of Oncology. 2016; 27: 1449–1455.
 Lastwika KJ, Wilson W, Li QK, Norris J, Xu H, Ghazarian SR, et al. Control of PD-L1 expression by oncogenic activation of the AKT–mTOR pathway in non–small cell lung cancer. Cancer Research. 2016; 76: 227–238.
 Liu X, Xiao M, Zhang L, Li L, Zhu G, Shen E, et al. The m6a methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. Journal of Clinical Laboratory Analysis. 2021; 35: e23655.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.