Single‐cell RNA sequencing reveals the niche transitions in the non‐small cell lung cancer microenvironment mediated by piR‐hsa‐164586 during the invasive and metastatic processes

Abstract Screening of tumor‐specific markers and targeted therapy has achieved significant clinical efficacy in recent years. PIWI‐interacting RNAs (piRNAs), which are crucial in the progression of tumors, are anticipated to be significant targets for the research and development of tumor molecular drugs aimed at tumors. This study corroborated the role of piR‐hsa‐164586 in enhancing the invasion and metastasis of non‐small cell lung cancer (NSCLC) cells, as previously observed with its unusually high expression in NSCLC tissue and serum extracellular vesicles, through both in vitro and in vivo experiments. Single‐cell RNA sequencing (scRNA‐seq) combined with other molecular techniques revealed that the overexpression of piR‐hsa‐164586 regulates the tumor niche of NSCLC by upregulating mesenchymal subtypes of tumor epithelial cells. Furthermore, piR‐hsa‐164586 is involved in regulating PI3K‐AKT pathway and epithelial–mesenchymal transition, thereby accelerating the invasion and metastasis of NSCLC cells. MYH9 (a non‐PIWI protein) could bind to piR‐hsa‐164586 and the knockdown of piR‐hsa‐164586 or MYH9 links to better NSCLC prognoses. In conclusion, this work not only revealed the specific regulatory mechanism of piR‐hsa‐164586 as a tumor marker of NSCLC, but also provided support for developing molecular targeted therapies for NSCLC.