Yaqian Liu1, Bo Pan1, Weikun Qu2, Yilong Cao1, Jun Li3, Haidong Zhao4. 1. Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, China. 2. Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, China. 3. Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, China. dyeylj@hotmail.com. 4. Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, China. z.hddl@hotmail.com.
Abstract
BACKGROUND: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated. METHODS: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound-healing and transwell migration assay. RESULTS: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. CONCLUSION: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
BACKGROUND:Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated. METHODS: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound-healing and transwell migration assay. RESULTS: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. CONCLUSION: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancerpatients.
Entities:
Keywords:
Bioinformatics analysis; Biomarkers; Breast cancer; F-box protein; Prognosis
Authors: Laszlo Radvanyi; Devender Singh-Sandhu; Scott Gallichan; Corey Lovitt; Artur Pedyczak; Gustavo Mallo; Kurt Gish; Kevin Kwok; Wedad Hanna; Judith Zubovits; Jane Armes; Deon Venter; Jalil Hakimi; Jean Shortreed; Melinda Donovan; Mark Parrington; Pamela Dunn; Ray Oomen; James Tartaglia; Neil L Berinstein Journal: Proc Natl Acad Sci U S A Date: 2005-07-25 Impact factor: 11.205
Authors: Antoine E Karnoub; Ajeeta B Dash; Annie P Vo; Andrew Sullivan; Mary W Brooks; George W Bell; Andrea L Richardson; Kornelia Polyak; Ross Tubo; Robert A Weinberg Journal: Nature Date: 2007-10-04 Impact factor: 49.962
Authors: Simon A Forbes; David Beare; Harry Boutselakis; Sally Bamford; Nidhi Bindal; John Tate; Charlotte G Cole; Sari Ward; Elisabeth Dawson; Laura Ponting; Raymund Stefancsik; Bhavana Harsha; Chai Yin Kok; Mingming Jia; Harry Jubb; Zbyslaw Sondka; Sam Thompson; Tisham De; Peter J Campbell Journal: Nucleic Acids Res Date: 2016-11-28 Impact factor: 16.971
Authors: Tomeka L Suber; Ina Nikolli; Michael E O'Brien; James Londino; Jing Zhao; Kong Chen; Rama K Mallampalli; Yutong Zhao Journal: Respir Res Date: 2018-10-25