Table 2.

The downstream therapeutic targets of TGF-β signaling in fibrotic microenvironment.

Factor	Mediators	Effect After Inhibition	Ref.
MicroRNAs (miRNAs)	miR-21	Decreases ECM synthesis and fibrosis via upregulation of MMP-9 expression	[154]
	miR-200	Protects TGF-β-mediated EMT by inhibiting the expression of ZEB 1 and 2	[155]
Long non-coding RNAs (LncRNAs)	Lnc-LFAR1	Downregulates TGF-β/Smad signaling pathway cancer cell proliferation	[156]
		Blocks tissue fibrosis by reducing Smad2/3 phosphorylation and binding to TGFβR1	[157]
	Lnc-TSI	Upregulates the interaction between Smad3 and TGFβR1 lead to cancer metastasis	[158]
	LncRNA H19X	Reduces ECM synthesis induced by TGF-β and controls the differentiation and survival of ECM-producing myofibroblasts	[159]
	Erbb4-IR	Supresses miR-29b transcription and consequent antifibrotic function	[68]
		Downregulates miRNA-145 to reduce cancer cell proliferation	[144]
Transcription factors (TFs)	Twist	Increases sensitivity to chemotherapy by downregulating MDR1 and reducing drug efflux	[160]
	ZEB1	Reduces antifibrotic miR200c and miR141 expression	[142]
		Reverses metastasis and restores chemosensitivity in chronic chemoresistant	[161]
		Reduces chemoresistance mediated by MGMT	[162]
		Restores miR-203 expression, supresses stemness and promotes chemo-sensitivity	[163]
	Pou4f1	Prevents macrophage-myofibroblast transition, thereby supressing MMT-mediated fibrosis	[140,164]