Recently, Professor Gao Peng's team from the Department of Pathology, School of Basic Medical Sciences, Shandong University, published a paper titled "Low glucose-induced overexpression of HOXC-AS3 promotes metabolic reprogramming of breast cancer" in Cancer Research, an international journal of oncology (District 1, Chinese Academy of Sciences, 5-year IF: 12.84). The research revealed a new mechanism of metabolic reprogramming in breast cancer (BC). Zhu Wenjie, a doctoral candidate at the School of Basic Medical Sciences of Shandong University, is the first author, and Professor Gao Peng of the School of Basic Medical Sciences is the corresponding author. Shandong University is the first author institute and the only corresponding author institute.

BC had replaced lung cancer as the most common tumor worldwide. However, the mechanisms underlying BC energy metabolism and progression remain obscure. Only 2% of human genomic DNA transcripts are translated into proteins, while the remaining 98% are called non-coding RNAs (ncRNAs). The long noncoding RNAs (lncRNAs) is a kind of ncRNA with a length of more than 200 bp. In this paper, they characterized a lncRNA HOXC-AS3, which was activated under glucose deprivation pressure, thus triggering a nutrient-stress response and a switch in glucose metabolism. Specifically, they identified that HOXC-AS3 selectively antagonize SIRT6-mediated H3K9ac deacetylation of glycolysis-related genes. Moreover, HOXC-AS3-occupied SIRT6 lost contact inhibition of HIF1α, leading to reprogramming in metabolic pathways. Additionally, HOXC-AS3, SP1 and miR-1224-5p form a positive feedback loop to maintain the production of cancer-promoting signal. Furthermore, the administration of anti-HOXC-AS3-motif-RNAs effectively disrupted the interaction and blocked the function of HOXC-AS3, ultimately suppressing BC progression. These results reveal the critical role of HOXC-AS3 in regulating metabolic reprogramming of BC cells under metabolic stress, indicating that HOXC-AS3 is a potential therapeutic target and using anti-HOXC-AS3-motif RNA mixture is a promising strategy to suppress BC progression.

Professor Gao Peng's research team has been committed to the study of tumor gene changes and expression regulation. In recent years, related papers have been published in Cell Death & Differentiation (1 paper, IF 15.8), Cancer Research (2 papers, IF 12.8), Journal of Hepatology (IF 25.1), Oncogene (6 papers; IF 9.87), Journal of Pathology (3 papers; top journals of pathology, IF 7.99), Cancer Letters (4 papers; IF 8.67) and other well-known journals.

The research was funded by the General Program of the National Natural Science Foundation of China, the Taishan Scholar Distinguished Professor Program and the Shandong Province New and Old Kinetic Energy Transformation Major Project.

Link to the article:https://pubmed.ncbi.nlm.nih.gov/35031573/.