LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis
© 2023. The Author(s)..
BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear.
METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis.
RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC.
CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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Enthalten in: |
Journal of translational medicine - 21(2023), 1 vom: 26. Nov., Seite 854 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ding, Yuqin [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 28.11.2023 Date Revised 07.03.2024 published: Electronic Citation Status MEDLINE |
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doi: |
10.1186/s12967-023-04640-3 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM36499939X |
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100 | 1 | |a Ding, Yuqin |e verfasserin |4 aut | |
245 | 1 | 0 | |a LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis |
264 | 1 | |c 2023 | |
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500 | |a Date Revised 07.03.2024 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2023. The Author(s). | ||
520 | |a BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear | ||
520 | |a METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis | ||
520 | |a RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC | ||
520 | |a CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Breast cancer | |
650 | 4 | |a Competing endogenous RNA | |
650 | 4 | |a Progression | |
650 | 4 | |a TDRKH-AS1 | |
650 | 4 | |a lncRNA | |
650 | 7 | |a MicroRNAs |2 NLM | |
650 | 7 | |a RNA, Long Noncoding |2 NLM | |
650 | 7 | |a Cyclic AMP Response Element-Binding Protein |2 NLM | |
650 | 7 | |a TDRKH protein, human |2 NLM | |
650 | 7 | |a RNA-Binding Proteins |2 NLM | |
650 | 7 | |a CREB1 protein, human |2 NLM | |
650 | 7 | |a MIRN134 microRNA, human |2 NLM | |
700 | 1 | |a Huang, Yuting |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Fanrong |e verfasserin |4 aut | |
700 | 1 | |a Gong, Lijie |e verfasserin |4 aut | |
700 | 1 | |a Liang, Chenlu |e verfasserin |4 aut | |
700 | 1 | |a Ding, Kaijing |e verfasserin |4 aut | |
700 | 1 | |a He, Xiangming |e verfasserin |4 aut | |
700 | 1 | |a Ding, Xiaowen |e verfasserin |4 aut | |
700 | 1 | |a Chen, Yiding |e verfasserin |4 aut | |
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