Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway
Long noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-02-01
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| Series: | Non-coding RNA Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468054024001240 |
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| author | Bingyu Wang Wenbo Liu Buyun Song Yong Li Yingying Wang Bibo Tan |
| author_facet | Bingyu Wang Wenbo Liu Buyun Song Yong Li Yingying Wang Bibo Tan |
| author_sort | Bingyu Wang |
| collection | DOAJ |
| description | Long noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of LINC00665 was correlated with poor prognosis. LINC00665 knockdown was verified to suppress migration, invasion, and resistance to trastuzumab in GC. Furthermore, we found that LINC00665 participates in the infiltration of naive B cells, mast cells, and T follicular helper (Tfh) cells. Mechanistically, LINC00665 was confirmed to regulate tumorigenesis and trastuzumab resistance by activating PI3K/AKt pathway. LINC00665 sponged miR-199b-5p to interact with SERPINE1 expression, resulting in the increase of phosphorylation of AKt, thus participating in the PI3K/AKt pathway. To summarize, LINC00665 facilitated the tumorigenesis and trastuzumab resistance of GC by sponging miR-199b-5p and promoting SERPINE1 expression, which further activated PI3K/AKt signaling; this finding reveals a new mechanism by which LINC00665 modulates tumor development and drug resistance in GC. |
| format | Article |
| id | doaj-art-7623c428cf084cd0bf63bbd2ebf4e380 |
| institution | OA Journals |
| issn | 2468-0540 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Non-coding RNA Research |
| spelling | doaj-art-7623c428cf084cd0bf63bbd2ebf4e3802025-08-20T02:04:38ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402025-02-011015316210.1016/j.ncrna.2024.07.004Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathwayBingyu Wang0Wenbo Liu1Buyun Song2Yong Li3Yingying Wang4Bibo Tan5The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaThe Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaThe Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaThe Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaThe Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaCorresponding author.; The Third Department of Surgery, The Fourth Hospital of Hebei Medical University, 050017, Shijiazhuang, ChinaLong noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of LINC00665 was correlated with poor prognosis. LINC00665 knockdown was verified to suppress migration, invasion, and resistance to trastuzumab in GC. Furthermore, we found that LINC00665 participates in the infiltration of naive B cells, mast cells, and T follicular helper (Tfh) cells. Mechanistically, LINC00665 was confirmed to regulate tumorigenesis and trastuzumab resistance by activating PI3K/AKt pathway. LINC00665 sponged miR-199b-5p to interact with SERPINE1 expression, resulting in the increase of phosphorylation of AKt, thus participating in the PI3K/AKt pathway. To summarize, LINC00665 facilitated the tumorigenesis and trastuzumab resistance of GC by sponging miR-199b-5p and promoting SERPINE1 expression, which further activated PI3K/AKt signaling; this finding reveals a new mechanism by which LINC00665 modulates tumor development and drug resistance in GC.http://www.sciencedirect.com/science/article/pii/S2468054024001240Gastric cancerLong non-coding RNAPI3K/AKt signalingDrug resistanceTargeted therapyceRNA |
| spellingShingle | Bingyu Wang Wenbo Liu Buyun Song Yong Li Yingying Wang Bibo Tan Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway Non-coding RNA Research Gastric cancer Long non-coding RNA PI3K/AKt signaling Drug resistance Targeted therapy ceRNA |
| title | Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway |
| title_full | Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway |
| title_fullStr | Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway |
| title_full_unstemmed | Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway |
| title_short | Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway |
| title_sort | targeting linc00665 mir 199b 5p serpine1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via pi3k akt pathway |
| topic | Gastric cancer Long non-coding RNA PI3K/AKt signaling Drug resistance Targeted therapy ceRNA |
| url | http://www.sciencedirect.com/science/article/pii/S2468054024001240 |
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