Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications

Abstract

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.

Keywords: anti-cancer metastasis; cancer biomarkers; extracellular vesicles; noncoding RNAs; organ-specific metastasis.

Figure 1

Tumor cell-derived EVs mediate organ-specific metastasis. Primary tumor cells secrete EVs into circulation as messengers, which spread and colonize to different metastatic sites, including bone, liver, lung, brain, and lymph nodes.

Figure 2

Tumor cell-derived EVs transfer different ncRNAs to induce organ-specific metastasis. Primary tumor cell-derived EVs deliver ncRNAs to specific organs or sites, which mediate organ-specific metastasis, including bone metastasis (A), liver metastasis (B), lung metastasis (C), brain metastasis (D), and lymphatic metastasis (E).