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Review
. 2024 Jun;29(6):89.
doi: 10.3892/mmr.2024.13213. Epub 2024 Apr 5.

Research progress on oncoprotein hepatitis B X‑interacting protein (Review)

Lei Cheng  1 , Lijuan Guo  2 , Teng Zou  2 , Yisong Yang  2 , Ran Tao  3 , Shuangping Liu  2
Affiliations
Review

Research progress on oncoprotein hepatitis B X‑interacting protein (Review)

Lei Cheng et al. Mol Med Rep. 2024 Jun.

Abstract

Hepatitis B X‑interacting protein (HBXIP) is a membrane protein located on the lysosomal surface and encoded by the Lamtor gene. It is expressed by a wide range of tumor types, including breast cancer, esophageal squamous cell carcinoma and hepatocellular carcinoma, and its expression is associated with certain clinicopathological characteristics. In the past decade, research on the oncogenic mechanisms of HBXIP has increased and the function of HBXIP in normal cells has been gradually elucidated. In the present review, the following was discussed: The normal physiological role of the HBXIP carcinogenic mechanism; the clinical significance of high levels of HBXIP expression in different tumors; HBXIP regulation of transcription, post‑transcription and post‑translation processes in tumors; the role of HBXIP in improving the antioxidant capacity of tumor cells; the inhibition of ferroptosis of tumor cells and regulating the metabolic reprogramming of tumor cells; and the role of HBXIP in promoting the malignant progression of tumors. In conclusion, the present review summarized the existing knowledge of HBXIP, established its carcinogenic mechanism and discussed future related research on HBXIP.

Keywords: ferroptosis; hepatitis B X‑interacting protein; oxidative stress; post‑transcription; review; transcription; translation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Normal physiological effects of HBXIP. Activation of mTORC1 signaling promotes normal differentiation of ESCs. HBXIP is involved in DNA damage repair by activating ATM. In the normal adult pancreas, HBXIP is highly expressed in the pancreatic islets in comparison with other pancreatic tissue and promotes the transcription of insulin. HBXIP, hepatitis B X-interacting protein; mTORC1, mammalian _target of rapamycin complex 1; ESCs, embryonic stem cells; ATM, ataxia telangiectasia mutated; Chk2, checkpoint kinase; c-Fos, c-Fos proto-oncogene protein; PDX-1, programmed cell death 1 ligand 1; Neurod1, neuronal differentiation 1Gene; P, phosphorylated.
Figure 2.
Figure 2.
HBXIP regulates tumor cells at multiple levels. HBXIP promotes c-Myc histone demethylation through LSD-1 and binds to the MEK2 promoter to promote transcription. HBXIP directly promotes transcription via the miR-18b promoter. HBXIP modifies HIF-1α and c-Myc mRNA methylation through Mettl3. Micro RNAs and long non-coding RNAs can _target or be _targeted by HBXIP. HBXIP can regulate the malignant progression of tumors by acetylase, phosphorylase or promoting the separation of _target proteins from ubiquitin recognition receptors. LSD-1, lysine-specific demethylase 1; HIF-1α, hypoxia-inducible factor-1α; Mettl3, methyltransferase-like 3; HBXIP, hepatitis B X-interacting protein; Keap1, Kelch-like ECH associated protein 1; PVHL, The von-Hippel Lindau tumor suppressor; MEK2, MAP Kinase Kinase2; MEK1, MAP Kinase Kinase1; PD-L1, programmed death ligand 1; PCAF, P300/CBP-associated factor; m6A, N6-methyladenosine; c-Myc, Cellular-myelocytomatosis viral oncogene; c-Fos, c-Fos proto-oncogene protein; HMGA2, The high mobility group protein 2; Hotair, HOX transcript antisense RNA; HDAC6, Histone deacetylase 6; HOXB13, Homeobox B13; MST, STE20-like kinase 1; NMHC-IIA, non-muscle heavy chain myosin IIA; SCD2, synthetic cytochrome c oxidase 2; PDHA1, pyruvate dehydrogenase A1; H3K4, histone H3 Lysine 4 trimethylation; PKCβII, protein kinase βC.
Figure 3.
Figure 3.
Multiple positive feedback processes involving HBXIP. After HBXIP upregulates TNFR1, this activates the NF-κB pathway, which activates STAT3 in the nucleus and activates the HBXIP promoter. After HBXIP upregulates LXRs, activated SREBP-1c stimulates the HBXIP promoter. HBXIP inhibits the inhibitory effect of Lin28b on Mettl3, which methylates the HBXIP promoter to promote HBXIP expression. HBXIP, hepatitis B X-interacting protein; Lin28b, Lin-28 homolog B; TNFR1, tumor necrosis factor receptor 1; NF-κB, nuclear factor-kB; STAT3, signal transducer and activator of transcription 3; LXRs, liver X receptor; Mettl3, methyltransferase-like 3; SREBP-1c, sterol regulatory element-binding transcription factor 1.
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