TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression
Background Renal cell carcinoma (RCC) originates from renal tubular epithelial cells and is mainly classified into three histological types, including clear cell renal cell carcinoma (ccRCC) which accounts for about 75% of all kidney cancers and is characterized by its strong invasiveness and poor p...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2023-10-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/16316.pdf |
| _version_ | 1797416833645543424 |
|---|---|
| author | Lingling Xie Yu Fang Jianping Chen Wei Meng Yangbo Guan Wenliang Gong |
| author_facet | Lingling Xie Yu Fang Jianping Chen Wei Meng Yangbo Guan Wenliang Gong |
| author_sort | Lingling Xie |
| collection | DOAJ |
| description | Background Renal cell carcinoma (RCC) originates from renal tubular epithelial cells and is mainly classified into three histological types, including clear cell renal cell carcinoma (ccRCC) which accounts for about 75% of all kidney cancers and is characterized by its strong invasiveness and poor prognosis. Hence, it is imperative to understand the mechanisms underlying the occurrence and progression of ccRCC to identify effective biomarkers for the early diagnosis and the prognosis prediction. Methods The mRNA level of TTC13 was quantified by RT-PCR, while the protein level was determined by western blot and immunohistochemistry (IHC) staining. Cell proliferation was measured by cck-8, and cell apoptosis was detected by flow cytometry. The binding of STAT3 to the promoter region of TTC13 was determined by the luciferase reporter assay and chip experiments. STAT3 nuclear translocation was assessed by immunofluorescence staining. Results We found that TTC13 was up-regulated in ccRCC, and TTC13 promoted cell proliferation as well as inhibited cell apoptosis and autophagy of ccRCC through wnt/β-catenin and IL6-JAK-STAT3 signaling pathways. Furthermore, TTC13 might play a role in the immune infiltration and immunotherapy of ccRCC. Mechanistically, STAT3 activated the transcription of TTC13 gene. Conclusions STAT3 directly regulated TTC13 expression through a positive feedback loop mechanism to promote ccRCC cell proliferation as well as reduce cell apoptosis and autophagy. These findings suggested new and effective therapeutic targets for more accurate and personalized treatment strategies. |
| first_indexed | 2024-03-09T06:09:54Z |
| format | Article |
| id | doaj.art-f0d2b8d097104af6bb915528dc46c0f8 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:09:54Z |
| publishDate | 2023-10-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-f0d2b8d097104af6bb915528dc46c0f82023-12-03T12:00:06ZengPeerJ Inc.PeerJ2167-83592023-10-0111e1631610.7717/peerj.16316TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progressionLingling Xie0Yu Fang1Jianping Chen2Wei Meng3Yangbo Guan4Wenliang Gong5Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Urology, The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Shanghai, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Urology, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Urology, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Urology, The First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Shanghai, ChinaBackground Renal cell carcinoma (RCC) originates from renal tubular epithelial cells and is mainly classified into three histological types, including clear cell renal cell carcinoma (ccRCC) which accounts for about 75% of all kidney cancers and is characterized by its strong invasiveness and poor prognosis. Hence, it is imperative to understand the mechanisms underlying the occurrence and progression of ccRCC to identify effective biomarkers for the early diagnosis and the prognosis prediction. Methods The mRNA level of TTC13 was quantified by RT-PCR, while the protein level was determined by western blot and immunohistochemistry (IHC) staining. Cell proliferation was measured by cck-8, and cell apoptosis was detected by flow cytometry. The binding of STAT3 to the promoter region of TTC13 was determined by the luciferase reporter assay and chip experiments. STAT3 nuclear translocation was assessed by immunofluorescence staining. Results We found that TTC13 was up-regulated in ccRCC, and TTC13 promoted cell proliferation as well as inhibited cell apoptosis and autophagy of ccRCC through wnt/β-catenin and IL6-JAK-STAT3 signaling pathways. Furthermore, TTC13 might play a role in the immune infiltration and immunotherapy of ccRCC. Mechanistically, STAT3 activated the transcription of TTC13 gene. Conclusions STAT3 directly regulated TTC13 expression through a positive feedback loop mechanism to promote ccRCC cell proliferation as well as reduce cell apoptosis and autophagy. These findings suggested new and effective therapeutic targets for more accurate and personalized treatment strategies.https://peerj.com/articles/16316.pdfTTC13Clear cell renal cell carcinomaBiomarkerImmunityPrognosisCell autophagy |
| spellingShingle | Lingling Xie Yu Fang Jianping Chen Wei Meng Yangbo Guan Wenliang Gong TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression PeerJ TTC13 Clear cell renal cell carcinoma Biomarker Immunity Prognosis Cell autophagy |
| title | TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression |
| title_full | TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression |
| title_fullStr | TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression |
| title_full_unstemmed | TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression |
| title_short | TTC13 expression and STAT3 activation may form a positive feedback loop to promote ccRCC progression |
| title_sort | ttc13 expression and stat3 activation may form a positive feedback loop to promote ccrcc progression |
| topic | TTC13 Clear cell renal cell carcinoma Biomarker Immunity Prognosis Cell autophagy |
| url | https://peerj.com/articles/16316.pdf |
| work_keys_str_mv | AT linglingxie ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression AT yufang ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression AT jianpingchen ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression AT weimeng ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression AT yangboguan ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression AT wenlianggong ttc13expressionandstat3activationmayformapositivefeedbacklooptopromoteccrccprogression |