Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer
BackgroundOvarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1055648/full |
| _version_ | 1811185693679943680 |
|---|---|
| author | Jie Li Zhefeng Li Yan Gao Hongyu Zhao Jiahao Guo Zhibin Liu Chenghong Yin Xiaoting Zhao Wentao Yue |
| author_facet | Jie Li Zhefeng Li Yan Gao Hongyu Zhao Jiahao Guo Zhibin Liu Chenghong Yin Xiaoting Zhao Wentao Yue |
| author_sort | Jie Li |
| collection | DOAJ |
| description | BackgroundOvarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence similarity 83 member D (FAM83D) in ovarian cancer by integrating single-cell RNA sequencing (scRNA-seq) and a prognostic model.MethodsA 10x scRNA-seq analysis was performed on cells from normal ovary and high-grade serous ovarian cancer (HGSOC) tissue. The prognostic model was constructed by Lasso-Cox regression analysis. The biological function of FAM83D on cell growth, invasion, migration, and drug sensitivity was examined in vitro in OC cell lines. Luciferase reporter assay was performed for binding analysis between FAM83D and microRNA-138-5p (miR-138-5p).ResultsOur integrative analysis identified a subset of malignant epithelial cells (C1) with epithelial-mesenchymal transition (EMT) and potential hyperproliferation gene signature. A FAM83D+ malignant epithelial subcluster (FAM83D+ MEC) was associated with cell cycle regulation, apoptosis, DNA repair, and EMT activation. FAM83D resulted as a viable prognostic marker in a prognostic model that efficiently predict the overall survival of OC patients. FAM83D downregulation in SKOV3 and A2780 cells increased cisplatin sensitivity, reducing OC cell proliferation, migration, and invasion. MiR-138-5p was identified to regulate FAM83D’s carcinogenic effect in OC cells.ConclusionsOur findings highlight the importance of miR-138 -5p/FAM83D/EMT signaling and may provide new insights into therapeutic strategies for OC. |
| first_indexed | 2024-04-11T13:33:33Z |
| format | Article |
| id | doaj.art-b521e37dd3c343459de2a889bdc0bc50 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T13:33:33Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b521e37dd3c343459de2a889bdc0bc502022-12-22T04:21:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.10556481055648Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancerJie Li0Zhefeng Li1Yan Gao2Hongyu Zhao3Jiahao Guo4Zhibin Liu5Chenghong Yin6Xiaoting Zhao7Wentao Yue8Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaDepartment of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, ChinaBackgroundOvarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence similarity 83 member D (FAM83D) in ovarian cancer by integrating single-cell RNA sequencing (scRNA-seq) and a prognostic model.MethodsA 10x scRNA-seq analysis was performed on cells from normal ovary and high-grade serous ovarian cancer (HGSOC) tissue. The prognostic model was constructed by Lasso-Cox regression analysis. The biological function of FAM83D on cell growth, invasion, migration, and drug sensitivity was examined in vitro in OC cell lines. Luciferase reporter assay was performed for binding analysis between FAM83D and microRNA-138-5p (miR-138-5p).ResultsOur integrative analysis identified a subset of malignant epithelial cells (C1) with epithelial-mesenchymal transition (EMT) and potential hyperproliferation gene signature. A FAM83D+ malignant epithelial subcluster (FAM83D+ MEC) was associated with cell cycle regulation, apoptosis, DNA repair, and EMT activation. FAM83D resulted as a viable prognostic marker in a prognostic model that efficiently predict the overall survival of OC patients. FAM83D downregulation in SKOV3 and A2780 cells increased cisplatin sensitivity, reducing OC cell proliferation, migration, and invasion. MiR-138-5p was identified to regulate FAM83D’s carcinogenic effect in OC cells.ConclusionsOur findings highlight the importance of miR-138 -5p/FAM83D/EMT signaling and may provide new insights into therapeutic strategies for OC.https://www.frontiersin.org/articles/10.3389/fonc.2022.1055648/fullovarian cancersingle-cell RNA sequencingbioinformaticsprognostic signatureFAM83D |
| spellingShingle | Jie Li Zhefeng Li Yan Gao Hongyu Zhao Jiahao Guo Zhibin Liu Chenghong Yin Xiaoting Zhao Wentao Yue Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer Frontiers in Oncology ovarian cancer single-cell RNA sequencing bioinformatics prognostic signature FAM83D |
| title | Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer |
| title_full | Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer |
| title_fullStr | Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer |
| title_full_unstemmed | Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer |
| title_short | Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer |
| title_sort | integrating single cell rna sequencing and prognostic model revealed the carcinogenicity and clinical significance of fam83d in ovarian cancer |
| topic | ovarian cancer single-cell RNA sequencing bioinformatics prognostic signature FAM83D |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1055648/full |
| work_keys_str_mv | AT jieli integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT zhefengli integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT yangao integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT hongyuzhao integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT jiahaoguo integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT zhibinliu integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT chenghongyin integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT xiaotingzhao integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer AT wentaoyue integratingsinglecellrnasequencingandprognosticmodelrevealedthecarcinogenicityandclinicalsignificanceoffam83dinovariancancer |