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Breast cancer is the most prevalent malignancy and the most significant contributor to mortality in female oncology patients. Potassium Two Pore Domain Channel Subfamily K Member 1 (KCNK1) is differentially expressed in a variety of tumors, but the mechanism of its function in breast cancer is unknown. In this study, we found for the first time that KCNK1 was significantly up-regulated in human breast cancer and was correlated with poor prognosis in breast cancer patients. KCNK1 promoted breast cancer proliferation, invasion, and metastasis in vitro and vivo. Further studies unexpectedly revealed that KCNK1 increased the glycolysis and lactate production in breast cancer cells by binding to and activating lactate dehydrogenase A (LDHA), which promoted histones lysine lactylation to induce the expression of a series of downstream genes and LDHA itself. Notably, increased expression of LDHA served as a vicious positive feedback to reduce tumor cell stiffness and adhesion, which eventually resulted in the proliferation, invasion, and metastasis of breast cancer. In conclusion, our results suggest that KCNK1 may serve as a potential breast cancer biomarker, and deeper insight into the cancer-promoting mechanism of KCNK1 may uncover a novel therapeutic target for breast cancer treatment. KCNK1 is a potassium channel differentially expressed in many tumors, but the mechanisms underlying its function in breast cancer remain unclear. This study shows that KCNK1 is overexpressed in breast cancer promoting proliferation, invasion and metastasis by increasing glycolysis and activating Lactate Dehydrogenase A. [ABSTRACT FROM AUTHOR]

In eukaryotes, alternative splicing refers to a process via which a single precursor RNA (pre-RNA) is transcribed into different mature RNAs. Thus, alternative splicing enables the translation of a limited number of coding genes into a large number of proteins with different functions. Although, alternative splicing is common in normal cells, it also plays an important role in cancer development. Alteration in splicing mechanisms and even the participation of non-coding RNAs may cause changes in the splicing patterns of cancer-related genes. This article reviews the latest research on alternative splicing in cancer, with a view to presenting new strategies and guiding future studies related to pathological mechanisms associated with cancer., Competing Interests: None., (AJCR Copyright © 2021.)