CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway
Bladder cancer (BC) is the second most common urinary system malignant tumor around the whole world. It has been reported that CNN1 was lowly expressed in BC tissues. However, the mechanisms of CNN1 on BC cells were unclear. Herein, we aimed to probe the specific influences of CNN1 on BC pathogenesi...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.859707/full |
| _version_ | 1811296928742244352 |
|---|---|
| author | Zheng Zhang Xiaoqing Li Shaokun Ren Wei Zhang |
| author_facet | Zheng Zhang Xiaoqing Li Shaokun Ren Wei Zhang |
| author_sort | Zheng Zhang |
| collection | DOAJ |
| description | Bladder cancer (BC) is the second most common urinary system malignant tumor around the whole world. It has been reported that CNN1 was lowly expressed in BC tissues. However, the mechanisms of CNN1 on BC cells were unclear. Herein, we aimed to probe the specific influences of CNN1 on BC pathogenesis. First, the expression level and prognostic ability of CNN1 in BC patients were surveyed. Then, CNN1 overexpression was executed to exhibit the influences of CNN1 on BC cells. The real-time PCR and Western blotting were employed to detect by the mRNA and protein expression levels. CCK8 assay was utilized to examine cell proliferation, and transwell assay was executed to test cell invasion and migration. The corresponding kits were utilized to detect glucose absorption, lactate secretion, and ATP level. BC cells overexpressing CNN1 were utilized to establish a nude mouse xenograft tumor model, and the tumor volume and tumor weight were detected. Nude mouse tumor tissues were used for immunohistochemical experiments to test the expression levels of Ki-67 and CNN1. The outcomes indicated that CNN1 was significantly lowly expressed in BC tissues and cells. Besides, low expression of CNN1 might be concerned with poor prognosis. Moreover, overexpression of CNN1 repressed the proliferation, invasion, and migration of BC cells. Furthermore, CNN1 overexpression decreased the protein levels of glycolysis-related protein GLUT1 (glucose transporter 1), pyruvate kinase M2 (PKM2), and LDHA (lactate dehydrogenase A). Then, the decreased mRNA and protein levels of HIF-1α and PDK1 were identified after CNN1 overexpression. The in vivo assays verified the effects of aberrant expression of CNN1 in mice with BC. In conclusion, these findings suggested that CNN1 might modulate BC progression through activating HIF-1α pathway and CNN1 might be a promising marker for BC diagnosis. |
| first_indexed | 2024-04-13T05:56:37Z |
| format | Article |
| id | doaj.art-48571b942089478ea3ac90449d1fc083 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T05:56:37Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-48571b942089478ea3ac90449d1fc0832022-12-22T02:59:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.859707859707CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling PathwayZheng Zhang0Xiaoqing Li1Shaokun Ren2Wei Zhang3Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, ChinaPhase I Clinical Trial Department, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaTianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, ChinaTianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, ChinaBladder cancer (BC) is the second most common urinary system malignant tumor around the whole world. It has been reported that CNN1 was lowly expressed in BC tissues. However, the mechanisms of CNN1 on BC cells were unclear. Herein, we aimed to probe the specific influences of CNN1 on BC pathogenesis. First, the expression level and prognostic ability of CNN1 in BC patients were surveyed. Then, CNN1 overexpression was executed to exhibit the influences of CNN1 on BC cells. The real-time PCR and Western blotting were employed to detect by the mRNA and protein expression levels. CCK8 assay was utilized to examine cell proliferation, and transwell assay was executed to test cell invasion and migration. The corresponding kits were utilized to detect glucose absorption, lactate secretion, and ATP level. BC cells overexpressing CNN1 were utilized to establish a nude mouse xenograft tumor model, and the tumor volume and tumor weight were detected. Nude mouse tumor tissues were used for immunohistochemical experiments to test the expression levels of Ki-67 and CNN1. The outcomes indicated that CNN1 was significantly lowly expressed in BC tissues and cells. Besides, low expression of CNN1 might be concerned with poor prognosis. Moreover, overexpression of CNN1 repressed the proliferation, invasion, and migration of BC cells. Furthermore, CNN1 overexpression decreased the protein levels of glycolysis-related protein GLUT1 (glucose transporter 1), pyruvate kinase M2 (PKM2), and LDHA (lactate dehydrogenase A). Then, the decreased mRNA and protein levels of HIF-1α and PDK1 were identified after CNN1 overexpression. The in vivo assays verified the effects of aberrant expression of CNN1 in mice with BC. In conclusion, these findings suggested that CNN1 might modulate BC progression through activating HIF-1α pathway and CNN1 might be a promising marker for BC diagnosis.https://www.frontiersin.org/articles/10.3389/fonc.2022.859707/fullbladder cancerCNN1glycolysisHIF-1αoverexpression |
| spellingShingle | Zheng Zhang Xiaoqing Li Shaokun Ren Wei Zhang CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway Frontiers in Oncology bladder cancer CNN1 glycolysis HIF-1α overexpression |
| title | CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway |
| title_full | CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway |
| title_fullStr | CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway |
| title_full_unstemmed | CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway |
| title_short | CNN1 Represses Bladder Cancer Progression and Metabolic Reprogramming by Modulating HIF-1α Signaling Pathway |
| title_sort | cnn1 represses bladder cancer progression and metabolic reprogramming by modulating hif 1α signaling pathway |
| topic | bladder cancer CNN1 glycolysis HIF-1α overexpression |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.859707/full |
| work_keys_str_mv | AT zhengzhang cnn1repressesbladdercancerprogressionandmetabolicreprogrammingbymodulatinghif1asignalingpathway AT xiaoqingli cnn1repressesbladdercancerprogressionandmetabolicreprogrammingbymodulatinghif1asignalingpathway AT shaokunren cnn1repressesbladdercancerprogressionandmetabolicreprogrammingbymodulatinghif1asignalingpathway AT weizhang cnn1repressesbladdercancerprogressionandmetabolicreprogrammingbymodulatinghif1asignalingpathway |