TABLE 2.

The characteristics of the included studies.

No.	References	Identified miR	Cell line	miR effect on NSCLC development
1	Zhu et al. (6)	hsa-miR-142-5p	A549 and HCC827 cells	FGD5-AS1 inhibits hsa-miR-142-5p expression, and hsa-miR-142-5p downregulates PD-L1 expression in NSCLC cells. PD-L1 knockdown and hsa-miR-142-5p ectopic expression decreased the migration and invasion of cisplatin-resistance NSCLC cells; however, the transfection of hsa-miR-142-5p inhibitor reversed this anti-tumoral effect.
2	Yang et al. (18)	hsa-miR-155-5p and hsa-miR-194-5p	A549 and H1395 cells	CircCHST15 inhibits the expression of hsa-miR-155-5p and hsa-miR-194-5p; hsa-miR-155-5p and hsa-miR-194-5p decrease PD-L1 expression in NSCLC cells. Although hsa-miR-155-5p increases the proliferation and clonogenicity of NSCLC cells, hsa-miR-194-5p decreases their proliferation and clonogenicity.
3	Shao et al. (17)	hsa-miR-326	A549 and H1734 cells	hsa-miR-326 expression is reduced in human NSCLC cell lines, i.e., A549 and H1734, and H1975, compared to normal human epithelial lung cells. hsa-miR-326 expression level is substantially decreased in NSCLC tissues, and there is a negative association between PD-L1 and hsa-miR-326 expression in primary and metastatic NSCLC tissues. hsa-miR-326 ectopic expression downregulates the expression of PD-L1 and B7-H3 in NSCLC cells. The expression of TNF-α, IFN-γ, and IL-2 are increased in the supernatant of hsa-miR-326 overexpressed cells. However, IL-1β, IL-10, and TGF-β expression are decreased. Also, the TNF-α+IFN-γ+CD8+ T-cells population is increased after hsa-miR-326 ectopic expression. Although hsa-miR-326 ectopic expression does not alter the proliferation of tumoral cells, it decreases the migration of tumoral cells. However, hsa-miR-326 expression decreases tumor growth, metastasis, and PD-L1 expression in animal models. Besides, ectopic expression of hsa-miR-326 increases the infiltration of CD8 cells and TNF-α+IFN-γ+CD8+ T-cells population in tumor tissues in animal models.
4	Chen et al. (16)	hsa-miR-526b-3p	A549 and PC-9	miR-526b-3p is substantially decreased in cisplatin-resistant lung cancer tissues compared to cisplatin-sensitive tissues. Also, the expression of miR-526b-3p is substantially decreased in NSCLC cell lines, i.e., H1975, A549, and PC-9, compared to normal human epithelial lung cells. miR-526b-3p increases cisplatin chemosensitivity and decreases the migration and proliferation of NSCLC cells. Also, miR-526b-3p ectopic expression increases the population of CD8+ T-cells. Besides, miR-526b-3p ectopic expression decreases the expression of PD-L1, MDR1, c-Myc, and STAT3.
5	Wang et al. (42)	hsa-miR-34a-5p	95D	circRNA-002178, which is upregulated in tumoral cells compared to normal cells, sponges hsa-miR-34a-5p expression and liberates the PD-L1 mRNA from the inhibitory effect of hsa-miR-34a-5p. The exosomal plasmatic level of circRNA-002178 can be a useful diagnostic marker for LUAD patients (AUC = 0.9956, and P-value < 0.001). The exosomal circRNA-002178 transferred from tumoral cells is significantly enriched in the tumor-infiltrating CD8+ T-cells of affected patients and sponges hsa-miR-28-5p expression to increase PD-1 expression in CD8+ T-cells.
6	Song et al. (20)	hsa-miR-138-5p	A549	hsa-miR-138-5p inhibits NSCLC development, increases tumor-infiltrating mature DCs, CD4+ T-cells, and CD8+ T-cells, and decreases tumor cell proliferation and tumor-infiltrating regulatory DCs. hsa-miR-138-5p downregulates the protein expression of tumor-intrinsic PD-L1 expression and PD-1 and PD-L1 expression in tumor-infiltrating DCs. However, hsa-miR-138-5p does not affect the mRNA expression of tumor-intrinsic PD-L1 in A549 and 3LL cells. hsa-miR-138-5p decreases PD-1 expression in DCs and T-cells, and miR-138-5p increases the ability of DC to induce cytotoxicity of CD8+ T-cells and promote the proliferation of CD4+ and CD8+ T-cells.
7	Li et al. (46)	hsa-miR-377-3p	A549	circRNA_0000284 targets hsa-miR-377-3p to increase PD-L1 expression. circRNA_0000284 expression is upregulated in NSCLC tissues compared to non-tumoral adjacent tissues, in higher stage (stage III and stage IV) tumor tissues than lower stage (stage I and stage II) tumor tissues, and in tissues with lymph node metastasis than tissues without lymph node metastasis. The increased expression of circRNA_0000284 has been associated with the decreased overall survival rate of affected patients. hsa-miR-377-3p targets tumor-intrinsic mRNA and protein PD-L1 expression in A549 and H82 cells. The pro-tumoral effect of circRNA_0000284 on cell proliferation, colony formation, migration, and invasion is mediated via the hsa-miR-377-3p/PD-L1 axis.
8	Katakura et al. (57)	hsa-miR-200b-5p	H460	hsa-miR-200b-5p inhibits tumor-intrinsic PD-L1 expression.
9	Kang et a. (44)	hsa-miR-34a-5p	A549 and H292	hsa-miR-34a-5p inhibitor increases tumor-intrinsic PD-L1 expression.
10	Huang et al. (53)	hsa-miR-155-5p	A549 and H1650	hsa-miR-155-5p inhibits tumor-intrinsic PD-L1 expression. Also, there is a negative correlation between hsa-miR-155-5p and PD-L1 expression in LUAD tissues.
11	Hong et al. (41)	hsa-let-7c-5p	A549 and H1299	circ-CPA4 targets hsa-let-7c-5p and liberate PD-L1 expression in NSCLC. In NSCLC tissues and cells, the expression of circ-CPA4 and PD-L1 is upregulated, and hsa-let-7c-5p expression is downregulated. Anti-PD-L1 antibodies interfere with the protective effect of the NSCLC cell-originated exosomes in cisplatin-induced cell death of NSCLC cancer cells. Tumor-intrinsic PD-L1 silencing or PD-L1/PD-1 blockade increased the proliferation and viability of CD8+ T-cells in a co-culture system. Besides, PD-L1 knockdown or blockade upregulated the expression of IFN-γ and IL-4 and downregulated IL-10 expressions in CD8+ T-cells.
12	Chen et al. (52)	hsa-miR-155-5p	A549	hsa-miR-155-5p inhibits tumor-intrinsic PD-L1 expression in NSCLC cells and decreases tumor cell proliferation. hsa-miR-155-5p increases the infiltration of IFN-γþ lymphocytes, CD4þ T lymphocytes, and CD8þ T lymphocytes. Also, hsa-miR-155-5p increases the expression of TNF-a and IFN-g and downregulates IL-10 expression.
13	Wei et al. (49)	hsa-miR-200a-3p	A549 and CAL-12T	MALAT1 sponges hsa-miR-200a-3p to liberate PD-L1 protein expression in NSCLC cells. MALAT1 overexpression increases cell proliferation, clonogenicity, migration, and invasion and decreases apoptosis in NSCLC cells; however, hsa-miR-200a-3p overexpression partially reverses the pro-tumoral effect of MALAT1 ectopic expression.
14	Dai Phung et al. (54)	hsa-miR-200c-3p	NCI-H1299	hsa-miR-200c-3p downregulates PD-L1 mRNA and protein expression in NSCLC cells. hsa-miR-200c-3p potentiates doxorubicin-induced cytotoxicity in NSCLC cells and substantially increases the cytotoxic T-cell-mediated killing against NSCLC cells and IFN-γ production.
15	Xie et al. (19)	hsa-miR-140	A549 and NCI-H1650	hsa-miR-140 downregulates protein and mRNA expression of PD-L1 in NSCLC cells. PD-L1-silencing or hsa-miR-140 ectopic expression downregulates cyclin-E protein and mRNA expression levels in NSCLC cells. Also, hsa-miR-140 overexpression arrests the cell cycle and decreases the proliferation of NSCLC cells.
16	Wan et al. (59)	hsa-miR-142-5p	A549	Increased expression of hsa-miR-142-5p inhibits PD-L1 expression in NSCLC cells. The overexpression of hsa-miR-142-5p increases tumor growth and decreases the apoptosis rate in NSCLCs, and anti-hsa-miR-142-5p ectopic expression has reversed these pro-tumoral effects.
17	Cortez et al. (43)	hsa-miR-34a-5p, hsa-miR-34b, and hsa-miR-34c-5p	A549, H460, and H1299	Increased expression of hsa-miR-34a-5p, hsa-miR-34b, and hsa-miR-34c-5p can inhibit PD-L1 protein expression in NSCLC cells.
18	Fujita et al. (55)	hsa-miR-197-3p	A549, and PC14	hsa-miR-197-3p is substantially downregulated in NSCLC cells compared to normal bronchial cells, and its ectopic expression enhances the chemosensitivity of NSCLC cells in vitro. hsa-miR-197-3p can suppress PD-L1 expression in NSCLC cells. The inhibition of hsa-miR-197-3p increases tumor growth and metastasis and worsens the survival of affected animal models.
19	Chen et al. (50)	hsa-miR-200b-3p and hsa-miR-200a-3p	H1299	hsa-miR-200b-3p and hsa-miR-200a-3p can downregulate PD-L1 expression in NSCLC cells.