Dataset Information

LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex.

ABSTRACT: There is no clear treatment guideline or individualized treatment plan for triple-negative breast cancer (TNBC). The aim of this study was to investigate more effective targets for TNBC-targeted therapy. MDA-MB-231 and BT549 cell lines were used to explore the function of LINC00649 on the proliferation, invasion, and migration of TNBC cells. A mice subcutaneous tumor model and a pulmonary metastasis model was established to identify the role of LINC00649 on the growth and metastasis of TNBC in vivo. LINC00649 was found to be a key molecule involved in the occurrence and development of TNBC by screening of public databases and detection of TNBC clinical samples. LINC00649 increased hypoxia-inducible factor 1α (HIF-1α) mRNA stability and protein expression by interacting with the nuclear factor 90 (NF90)/NF45 complex. In vitro, interference with LINC00649 inhibits MDA-MB-231 and BT549 cell proliferation, migration, and invasion, and the addition of HIF-1α revised this effect. In vivo experiments showed that LINC00649 promoted the growth and metastasis of TNBC. We demonstrated that LINC00649 interacts with the NF90/NF45 complex to increase the mRNA stability of HIF-1α and up-regulate HIF-1α expression, thereby inducing the proliferation, invasion, and migration of TNBC cells as well as tumor growth and metastasis.

SUBMITTER: Zhang J

PROVIDER: S-EPMC9037445 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex.

Zhang Jianhua J Du Chuang C Zhang Linfeng L Wang Yan Y Zhang Yingying Y Li Jingruo J

Cell cycle (Georgetown, Tex.) 20220221 10

There is no clear treatment guideline or individualized treatment plan for triple-negative breast cancer (TNBC). The aim of this study was to investigate more effective targets for TNBC-targeted therapy. MDA-MB-231 and BT549 cell lines were used to explore the function of LINC00649 on the proliferation, invasion, and migration of TNBC cells. A mice subcutaneous tumor model and a pulmonary metastasis model was established to identify the role of LINC00649 on the growth and metastasis of TNBC <i>i ...[more]

PMID: 35188449

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Project description:Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments-including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection-validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

Dataset Information

LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex.

Publications

LncRNA LINC00649 promotes the growth and metastasis of triple-negative breast cancer by maintaining the stability of HIF-1α through the NF90/NF45 complex.

Similar Datasets

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