Core Viewpoint - Triple-negative breast cancer (TNBC) is characterized by high metastasis rates, poor prognosis, and low survival rates, making it the most aggressive and deadly subtype of breast cancer. The lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) makes identifying specific therapeutic targets a pressing challenge in TNBC research [2]. Group 1 - Increasing evidence suggests that non-coding RNAs, such as circular RNA (circRNA) and long non-coding RNA (lncRNA), can encode functional peptides/proteins that play significant regulatory roles in physiological and pathological processes. In TNBC, some peptides encoded by non-coding RNAs have been confirmed to participate in key oncogenic processes, including tumor growth, metastasis, and the development of treatment resistance [2]. - A novel peptide, 66CTG, encoded by lncRNA, has been identified to stabilize the c-Myc proto-oncogene protein, promoting cancer growth in TNBC. This discovery provides a new potential biomarker and therapeutic target for TNBC diagnosis and treatment [3]. - The research team identified an upregulated lncRNA, CDKN2B-AS1, in TNBC, which encodes a 66-amino acid peptide through CUG initiation translation. The peptide 66CTG was confirmed to be endogenously expressed in TNBC cells through CRISPR-Cas9 gene editing and mass spectrometry analysis [6]. Group 2 - Mechanistically, during the late G1 phase of cell division, 66CTG stabilizes c-Myc through competitive interaction with FBW7α, an E3 ligase that mediates the ubiquitination and degradation of c-Myc [7]. - Overall, the findings suggest that 66CTG could be developed as a target for TNBC diagnosis and treatment. The study reveals a regulatory axis where 66CTG interacts with FBW7α to stabilize c-Myc, providing a new mechanistic explanation for the overexpression of c-Myc in TNBC. Patients with overexpression of 66CTG, c-Myc, and Cyclin D1 may benefit from targeted therapy along this signaling axis [9].