Regulatory role of LncRNA identified in Ca2+ Signaling-Mediated Tumor Microenvironment Remodeling

The research team led by LIN Aifu, a researcher at the College of Life Sciences, Zhejiang University, published a research paper entitled “LncRNACamK-A Regulates Ca2+ Signaling-Mediated Tumor Microenvironment Remodeling” in the September 13 issue of Molecular Cell.

The tumor microenvironment is the cellular environment in which the tumor exists. The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells. However, little is known regarding how the tumor responds to and remodels the microenvironment. Thus, it is of appreciable scientific importance to explore the remodeling mechanism of the tumor microenvironment and seek therapy for its regulation, which will tremendously facilitate the diagnosis and treatment of cancers.

Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, LIN Aifu et al. identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. 

Notably, this human-patient-derived xenograft (PDX) model demonstrates that targeting CamK-A robustly impaired cancer development.Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.