Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth

Abstract

BACKGROUND Abnormal tuftelin 1 (TUFT1) has been reported in multiple cancers and exhibits oncogenic roles in tumor progression. However, limited data are available on the relationship between TUFT1 and hepatocellular carcinoma (HCC), and the exact biological mechanism of TUFT1 is still poorly understood in HCC. AIM To investigate TUFT1 expression in HCC and how interfering TUFT1 transcription affects HCC growth. METHODS TUFT1 in HCC and non-HCC tissues based on databases of the Cancer Genome Atlas and Oncomine were analyzed, and TUFT1 in human HCC tissues on microarray were detected by immunohistochemistry for clinicopathological features, overall survival, and disease-free survival. HCC cells were transfected with constructed vectors of TUFT1 that interfere or over-express TUFT1 for analyzing the biological behaviors of HCC cells. Proliferation, invasion, migration, and apoptosis of cells were detected by cell counting kit-8, scratch assay, transwell tests, and flow cytometry and confirmed by Western blotting, respectively. RESULTS Abnormal TUFT1 levels in databases expressed in HCC at messenger RNA (mRNA) level and HCC tissues were mainly located in cytoplasm and membrane. The level of TUFT1 expression in the HCC group was significantly higher ( χ 2 = 18.563, P < 0.001) than that in the non-cancerous group, closely related to clinical staging, size, vascular invasion of tumor, hepatitis B e-antigen positive, and ascites ( P < 0.01) of HCC patients, and negatively to HCC patients’ overall survival and disease-free survival ( P < 0.001). After interfering with TUFT1 transcription at mRNA level in the MHCC-97H cells by the specific TUFT1-short hairpin RNA, cell proliferation, invasion, and metastasis were significantly inhibited with increasing apoptosis rate. In contrast, proliferation, invasion, and migration were significantly enhanced after over-expression of TUFT1 mRNA in Hep3B cells in vitro . CONCLUSION Oncogenic TUFT1 was associated with the progression of HCC and could be a potential molecular-target for inhibiting HCC growth.

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

“…One universal concept that has emerged from previous studies is that TUFT1 promotes cancer development and progression through different signaling pathways [ 66 , 67 , 68 , 69 , 70 ]. High expression of this protein is associated with poor prognosis in several types of cancer, including thyroid cancer [ 70 ], liver cancer [ 69 , 71 ], pancreatic cancer [ 66 ], gastric cancer [ 67 ], lung cancer [ 67 ], and breast cancer [ 67 , 72 ]. From this perspective, taking into account the enormous commitment of TUFT1 to carcinogenesis and its related processes, the lncRNA HNF1A-AS1/miR-34b/TUFT1 axis is a tempting exemplification of continuing research into targeted therapy aimed at inhibiting the release and transport of exosomes with high lncRNA HNF1A-AS1 expression [ 39 ].…”

The expression of tuftelin 1 as a new theranostic marker in early diagnosis and as a therapeutic target in hepatocellular carcinoma

“…As well as, TUFT1 is expressed in embryonic stem cells, neuronal cells, and other non‐mineralizing tissues like brain, eyes, lung, adrenal gland, liver, kidneys, testes, and tumor tissues 8,9 . Oncogenic TUFT1 was associated with HCC progression and could be a useful molecular‐target for inhibiting HCC growth 10 . Recently, it has been demonstrated for the first time that the expression of both TUFT 1‐mRNA, and protein was upregulated in HCC cells.…”

“…8,9 Oncogenic TUFT1 was associated with HCC progression and could be a useful molecular-target for inhibiting HCC growth. 10 Recently, it has been demonstrated for the first time that the expression of both TUFT 1-mRNA, and protein was upregulated in HCC cells. TUFT 1 upregulation was correlated with poor prognosis as well as unfavorable clinical outcomes in HCC patients via induction of HCC cell growth, epithelial-mesenchymal transition as well as metastasis which were verified in both in vitro and in vivo.…”

Tuftelin 1 Facilitates Hepatocellular Carcinoma Progression through Regulation of Lipogenesis and Focal Adhesion Maturation

“…In pancreatic cancer, TUFT1 was upregulated and promoted epithelial-mesenchymal transition through regulating HIF1-Snail pathway [ 28 ]. TUFT1 also participates in the regulation of HCC progression through different signaling pathways [ 29 , 30 ], whereas its interactome and functional mechanisms have not been fully unrevealed.…”