The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression

Table 1

Antitumour or protumourigenic effects elicited by the cellular components of TME in NSCLC through miRNA regulation.

Cellular component of TME	miRNA	Direct target of miRNA	Biological mechanisms	Ref.
Cancer-associated fibroblasts (CAFs)	miRNA-1	CXCL12	Downregulated the expression of CXCR4, NF-κB, and Bcl-xL in NSCLC cells and blocked lung cancer cell proliferation and drug resistance	[8]
	miRNA-101	CXCL12	Blocked the ability of CAFs to stimulate tumour cell proliferation, sphere formation, migration, and invasion and to increase apoptosis of NSCLC cells	[32]
	miRNA-1, miRNA-206	VEGFA/CCL2	Modified the tumour microenvironment generated by CAFs: by reducing tumour angiogenesis, TAM accumulation, tumour growth, and lung metastasis	[33]
	miRNA-31	FOXO3a	Increased VEGFA expression and lung cancer cells’ colony formation	[33]
Tumour-associated macrophages (TAMs)	miRNA-130-a	PPARγ	Skewed TAM polarization from an M2 toward an M1 phenotype	[42]
	miRNA-1207-5p	CSF1	Downregulated STAT3 and AKT signaling, resulting in reduced M2 macrophage characters (such as IL-10 and VEGF) and increased M1 macrophage characters (such as IL-12 and IL-23) in macrophage-like differentiated cells (d-THP1) that led to the attenuation of lung cancer growth and metastasis	[7]
	miRNA-103-a	PTEN	Activation of AKT and STAT3, leading to M2 macrophage polarization and increased proangiogenic factor expression	[44]
	miRNA-146-a	N/A	Blocked proinflammatory cytokines (IL-1β, IL-6, and TNF-α) resulting in the reduced antitumour ability of M1-like TAMs in response to TRAIL	[45]
Regulatory T cells (Tregs)	miRNA-141	CXCL1	Reduced recruitment of Tregs to the malignant pleural effusion of NSCLC patients, decreased immune escape of tumour cells, inhibited progression of pleural metastasis, and increased survival time of patients	[50]
CD4^+ tumour-infiltrating lymphocytes (TILs)	miRNA-155	N/A	Autophagy blockage in combination with carboplatin treatment increased miRNA-155 expression, leading to CD4^+, CD8^+, or Foxp3^+ regulatory T cell infiltration in the tumour microenvironment of NSCLC tissue samples; these phenomena were speculated to result in the inhibition of metastasis and restoration of chemoresistance in NSCLC	[51]
CD8^+ tumour-infiltrating lymphocytes (TILs)	miRNA 200b/a/429	PD-L1	Increased CD8^+ T cell infiltration, reversed exhausted CD8^+ T cell phenotype, reduced tumour burden, and metastases with mesenchymal lung tumours	[60]
Tumour-infiltrating natural killer (NK) cells	miRNA-183	DAP12	TGF-β induced miRNA-183 expression in NK cells that resulted in the silencing of tumour-associated NK cells	[68]
Dendritic cells	miRNA-301a	N/A	Induced an immunosuppressive microRNA signature in pulmonary DCs by decreasing IL-12 secretion, reducing IFN-γ released from CD8^+ T cells, and shifting the cytokine profile of CD4^+ T helper cells from IFN-γ-T cells to IL-13- and IL-17A-secreting T cells	[72]
	miRNA-31	N/A	Hypoxia drove intrinsic miR-31 expression in myeloid DCs. This resulted in the release of tumour-supporting soluble factors (S100A8, A100A9, and VEGF) and the increase in invasiveness of lung carcinoma cells, as indicated by morphological changes (loss of cellular sphericity and the appearance of filopodia-like protrusions)	[73]

Oncogenic miRNAs are indicated with an asterisk.