Figure 8. The proposed model of the miRNA-mediated intercellular communication mechanism.

The top panel depicted the cancer cell invasion to other cells in vinicty, possibly mediated by miRNA regulation of extracellular environment such as extracellular matrix (ECM) organization as well as receptor interactions such as focal adhesion. The bottom panel zooms into the tumor or tumor-transforming cell, which was drawn based on the KEGG pathways in cancers (hsa05200)³⁰ and the confidence recurrent miRNA regulatory network. Several important cancer signalling pathways possibly affected by miRNA dysregulation include Jak-STAT, VEGF, PI3K-Akt, mTOR, Wnt, p53, and TGF-β signalling pathways, which may drive phenotypic changes such as sustained angiogenesis, cell proliferation, evading apoptosis, insensitivity to anti-growth signals, and resistant to chemotherapy. On the other hand, intercellular interactions including cytokine-cytokine receptor interactions, ECM-receptor interactions, and focal adhesion are also likely to be mediated by miRNAs to facilitate tumor invasion. Also drawn is the transportation of the extracellular RNA (exRNA) via extracellular vesicles or exosomes¹⁶. It is possible that miRNAs not only mediate cell-to-cell communication by altering the ECM composition and receptor interactions but also serve as an effective communication means as tumorigenic messengers in the form of exRNA to infiltrate into adjacent cells⁴⁷. The exRNA transportation via exosomes may be in turn facilitated by the miRNA-related re-organization of the extracellular environment.