Abstract
BackgroundLong non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC.MethodsNext-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing.ResultsThe expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-β signaling to control TNBC progression.ConclusionADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-β signaling pathway.
Highlights
Breast cancer (BC) is a leading cause of cancer-related death in women [1]
Next-generation sequencing was conducted to compare the expression of different long ncRNAs (lncRNAs) in triple-negative BC (TNBC) tumor and paracancerous tissues, after which ADAMTS9AS2differential expression in these tumor tissues was evaluated via qPCR
The expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size
Summary
Breast cancer (BC) is a leading cause of cancer-related death in women [1]. While many advances in BC diagnosis and treatment have been made in recent years, high rates of tumor chemoresistance and metastasis often result in a poor prognosis [2]. LncRNAs are able to control transcription and translation [10,11,12], thereby regulating the progression of many tumor types including BC [13] by controlling cell survival, proliferation, metastasis, and chemoresistance [14, 15]. In BC, ADAMTS9‐ AS2 downregulation is linked to miR-130a-5p upregulation and tamoxifen resistance [18], while in ovarian cancer this lncRNA targets the miR-182-5p/FOXF2 signaling axis to control tumor progression [19]. Long non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. We explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC
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