Table 1.

Summary list of which HBx is involved in liver tumor microenvironment

Components	Effects	Study type	REFERENCES
Tumor cells	1. Promoting tumor cell proliferation	In vitro studies of transfected cell lines (HepG2) using JetPEI reagent	Cho et al. [7]
	2. Inhibiting apoptosis	In vitro studies of transfected cell lines HepG2 and HepG2.2.15 cells	Liu et al. [6]
	3. Inducing autophagy	In vitro studies of transfected cell lines human conjunctival epithelial Chang cells using Lipofectamine 2000 transfection reagent	Zhang et al. [16]
	4. Accelerating cell cycle progression.	In vitro studies of transfected cell lines Hep3B, Huh7, and HepG2 using CaPO4 precipitation method	Park et al. [5]
Immune cells	1. Promoting the apoptosis of CD8 + T lymphocytes	In vitro studies of isolated primary hepatocytes using	Lee et al. [17]
		recombinant baculovirus infection
	2. Decreasing the generation of IFN-γ
	3. Upregulation of major histocompatibility complex, ICAM-1,	In vitro studies of transfected cell lines HepG2 and UP74 cells	Zhou et al. [18]
	and Fas ligand	In vitro studies of transfected cell lines HepG2 and Huh7 cells	Kim et al. [19]
Hepatic stellate cells	1. Promoting hepatic stellate cell activation	In vitro studies of transfected cell lines hepatocyte cell lines Chang liver and HepG2 cells	Martin et al. [20]
	2. Promoting extracellular matrix remodeling, fibrosis
	angiogenesis, HCC invasion, and metastasis
	3. Promoting the proliferation of hepatic stellate cells	In vitro studies of transfected cell lines HepG2 and LX-2 using FuGENE HD transfection reagent	Bai et al. [21]
TGF-β	1. Upregulating TGF-β in a paracrine-dependent manner	In vitro studies of transfected cell lines hepatocyte cell lines Chang liver and HepG2 cells	Martin et al. [20]
	2. Participation in hepatic stellate cells activation	In vitro studies of transfected cell lines HL-7702 and L02 cells using a lipid-mediated method	Chen et al. [22]
	3. Transforming intrahepatic TGF-β signaling pathway from tumor-suppressive pSmad3C to tumor-supportive pSmad3L	In vivo studies of transgenic CD-1 mice and clinical specimens	Murata et al. [23]
	4. Cooperating with stem cell pathways to induce EMT	In vitro studies of transfected cell lines HMLE cell	Scheel et al. [24]
Interleukin family	1. Stimulating the production of IL-6 to mediate HCC development	In vitro studies of transfected cell lines L02 and SMMC-7721	Xiang et al. [25]
	2. Upregulating the expression of IL-8 to promote tumor growth and the malignant transformation of hepatocytes	In vitro studies of transfected cell lines SMMC-7721 and HepG2 cells	Wang et al. [26]
	3. Regulating other pro-inflammatory cytokines such as IL-18, IL-23, and TNF-α to induce liver chronic inflammation	In vivo studies of clinical specimens and in vitro studies of transfected cell lines HepG2 and Huh-7 cells	Xia et al. [27]
TNF-α	1. Upregulating TNF-α levels at transcriptional level	In vitro studies of transfected cell lines CCL13 and HepG2 cells	Lara-Pezzi et al. [28]
	2. Promoting tumor development and angiogenesis		Review [29]
COX-2	1. Upregulating the expression of MT1-MMP in a COX-2-dependent manner	In vitro studies of transfected cell lines CCL13 and HepG2.2.15 cell	Lara-Pezzi et al. [30]
	2. Exerting its anti-apoptotic effects by activating the COX-2/PGE(2) signaling pathway	In vitro studies of transfected cell lines Hep3B cell	Cheng et al. [31]
	3. Promoting tumor growth, invasion and metastasis	In vivo studies of clinical specimens and in vitro studies of transfected cell lines HepG2 cell	Liu et al. [32]
HIF-1α	1. Preventing HIF-1α degradation	In vitro studies of transfected cell lines CCL 13, HepG2, etc.	Yoo et al. [33, 34]
	2. Upregulating the expression of HIF-1α	In vitro studies of transfected cell lines Chang X-34 cells, HepG2, etc.	Yoo et al. [35]
Exosome	1. Negatively regulating the expression of exosomal miR-122	In vitro studies of transfected cell lines HepG2 and Huh-7 cell	Song et al. [36]
	2. Significantly altering the exosomal protein content	In vitro studies of transfected cell lines Huh-7 cell	Zhao et al. [37]