LINC01770 Is Associated with Stem-like Features and Aggressive Traits in Breast Cancer Cells Through a Putative miR-335-5p/OCT4 Axis.

Background/Objectives: Long non-coding RNAs (lncRNAs) are regulatory transcripts that contribute to diverse cellular processes and are increasingly recognized for their involvement in human diseases including cancer. In this context, long intergenic non-protein-coding RNA 1770 (LINC01770), also known as RRFERV, has been involved in nasopharyngeal cancer progression. However, its role in breast cancer (BC) remains unexplored. Here, we propose that LINC01770 plays a pivotal role in the development of aggressiveness traits such as invasion, migration, stemness, and tumorigenesis in BC cells. Methods: The LINC01770 overexpression was performed in BC cells using lentiviral transduction. Stemness and epithelial-mesenchymal transition markers, CD133+/44+ populations, cell migration, cell invasion, tumorigenesis in vitro, and chemoresistance were subsequently assessed via quantitative reverse transcription polymerase chain reaction (RT-qPCR), flow cytometry, Boyden chambers, soft agar, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. LINC01770 expression in BC tissues and mechanistic analyses were performed in silico. Results: LINC01770 promotes cell migration and invasion accompanied by increased expression of EMT-associated genes. Moreover, elevated LINC01770 levels lead to an expansion of CD133+/CD44+ cell populations and upregulation of stemness-related genes as well as increase tumorigenic capacity in vitro. In contrast, no significant effects on drug resistance were observed. Finally, bioinformatic analyses suggest a putative LINC01770/miR-335-5p/OCT4 regulatory axis, consistent with the observed increase in OCT4 expression after LINC01770 overexpression. Conclusions: Our findings demonstrate that LINC01770 drives BC progression by promoting migration, invasion, and stemness features via the miR-335-5p/OCT4 axis. To our knowledge, this is the first study identifying LINC01770 as a potential therapeutic target in BC.