Published online Jun 21, 2021. doi: 10.3748/wjg.v27.i23.3327
Peer-review started: December 14, 2020
First decision: December 27, 2020
Revised: January 6, 2021
Accepted: May 19, 2021
Article in press: May 19, 2021
Published online: June 21, 2021
Tuftelin 1 (TUFT1) has been reported to be elevated in multiple cancer types, and its abnormal expression has attracted medical attention as a novel oncogenic biomarker. However, the relationship between TUFT1 and hepatocellular carcinoma (HCC) remains to be identified. In this study, the levels of TUFT1 in HCC tissues were investigated and the roles of TUFT1 expression were explored in vitro by intervening in TUFT1 activation of HCC cell lines.
TUFT1 was first identified and sequenced from a bovine ameloblast-enriched complementary DNA library with a highly conserved gene localized in chromosome 1q21-31 that contained 13 exons, encoding an acidic, phosphorylated glycoprotein of 390 amino acids, and it plays a critical role in the development and mineralization of enamel. Recently, TUFT1 has been reported to be elevated in multiple cancers, and abnormal TUFT1 has attracted medical attention for HCC. However, limited data is available on the relationship between TUFT1 and HCC, and the exact biological mechanism of TUFT1 is still poorly understood in HCC.
The pathogenesis and feasible therapeutic treatments of HCC need urgent investigation. Abnormal TUFT1 has been reported in multiple cancers, and it exhibits oncogenic roles in tumor progression. In this study, the landscape of TUFT1 expression in human HCC tissues was investigated, and its mechanism was confirmed through intervening or over-expressing TUFT1 activation in vitro.
TUFT1 on databases of the Cancer Genome Atlas and Oncomine or in HCC tissues were analyzed for clinicopathological features, overall survival, and disease-free survival. High and low expressing HCC cell lines were screened among different HCC cell lines and transfected with constructed vectors that interfere or over-express TUFT1 to analyze biological behaviors. Proliferation, invasion, migration, and apoptosis of cells were detected by CCK-8, scratch assay, transwell tests, and flow cytometry, respectively, and confirmed by Western blotting.
The research results confirmed that TUFT1 was over-expressed in HCC tissues, and its expression was significantly related to tumor size, vascular invasion, positive hepatitis B e-antigen, advanced tumor-node-metastasis staging, ascites, shorter overall survival, and disease-free survival of HCC patients. Novel findings were that interfering with TUFT1 gene transcription could markedly suppress the proliferation and metastasis of the higher TUFT1 MHCC-97H cell lines through an apoptosis mechanism. Moreover, over-expressing TUFT1 promoted the growth and metastasis of the lower TUFT1 Hep3B cell lines in vitro.
Based on human specimen studies, high TUFT1 levels were associated with HCC progression, inhibiting TUFT1 affected proliferation and metastasis, over-expressing TUFT1 promoted proliferation and metastasis, and interfering activation of TUFT1 led to significant increase in cell apoptosis. TUFT1 could be a novel useful target for HCC effective therapy.
Basic and clinical studies have confirmed that the alterations of oncogenic TUFT1 expression might promote HCC growth and metastasis via an anti-apoptotic mechanism, and abnormal TUFT1 level could be a new prognostic marker or potential molecular target for HCC therapy. More studies in the future are needed to clarify the molecular mechanisms underlying TUFT1 up-regulation contribution to the progression of HCC.