Polymorphisms in ENAM, AMBN, and KLK4 predispose Egyptian adults to dental caries: A cross-sectional study.

Objective: This study investigates the distributional discrepancies of four single-nucleotide polymorphic loci as correlatives and causatives of dental caries susceptibility among Egyptians. Method: We conducted a cross-sectional study through the genotyping of enamelin (ENAM rs3796703), ameloblastin (AMBN rs4694075), tuftelin 1 (TUFT1 rs78802584), and kallikrein 4 (KLK4 rs2242670) in 132 adults (males = 74, females = 58) and 72 controls (males = 40, females = 32) referred from various Egyptian hospitals. For each participant, the number of decayed, missing, and filled teeth was charted, and the presence of biofilm/gingivitis/fluorosis was assessed. Bitewing radiographs were taken to detect interproximal caries. In addition, statistical analysis was conducted using Chi-square test, odds ratios, and corresponding P-values. Results: The alleles and genotypes of ENAM rs3796703, AMBN rs4694075, and KLK4 rs2242670 correlated strongly with dental caries susceptibility. However, TUFT1 rs78802584 did not exhibit such associations. Conclusion: These findings suggest the potential role of ENAM, AMBN, and KLK4 as determinants of dental caries susceptibility among Egyptian adults. The role of ENAM, AMBN, and KLK4 genetic variants is determinant in influencing susceptibility to dental caries in the Egyptian population, providing valuable insights into the genetic aspects of oral health. However, the lack of associations of caries susceptibility with TUFT1 rs78802584 contradicts its cariogenic role in many ethnicities.

Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat.

Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-Lx) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (Tuft1) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and ß-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the Tuft1 gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.NEW & NOTEWORTHY A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (Tuft1) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the Tuft1 gene.

microRNA-128-3p inhibits proliferation and accelerates apoptosis of gastric cancer cells via inhibition of TUFT1.

OBJECTIVE: Gastric cancer (GC) is a malignant tumor rooting in the gastric mucosal epithelium, ranking the first among various malignant tumors. Therefore, the influence of microRNA-128-3p (miR-128-3p) by regulation of Tuftelin1 (TUFT1) on GC cells was investigated. METHODS: The expression levels of miR-128-3p and TUFT1 in GC tissues and cells were detected. The correlation between miR-128-3p expression and overall survival of GC patients was analyzed. Human GC cells MGC803 were transfected with miR-128-3p or TUFT1-related oligonucleotides to figure their roles in viability, apoptosis, invasion, as well as epithelial-mesenchymal transition (EMT). The relationship between miR-128-3p and TUFT1 was validated. RESULTS: miR-128-3p expression was low and TUFT1 expression was high in GC tissues. miR-128-3p expression was positively correlated with the overall survival of patients with GC. miR-128-3p targeted TUFT1. Up-regulated miR-128-3p or suppressed TUFT1 repressed viability, invasion, and EMT, and accelerated apoptosis of GC cells. Overexpressed TUFT1 reduced miR-128-3p-mediated growth inhibition of GC cells. CONCLUSION: The study stresses that miR-128-3p can inhibit TUFT1 expression, thereby repressing GC cell activities.

Tuftelin 1 (TUFT1) Promotes the Proliferation and Migration of Renal Cell Carcinoma via PI3K/AKT Signaling Pathway.

Tuftelin 1 (TUFT1), a protein functioning distinctively in different tissues, is reported to be elevated in several types of cancers and the elevation of TUFT1 is correlated with unfavorable clinicopathologic characteristics and poor survival. However, the involvement of TUFT1 in renal cell carcinoma (RCC) remains unknown. In the current study, we investigated the role of TUFT1 in RCC and potential underlying mechanisms. RT-PCR and Western blot analysis showed that both the mRNA and protein levels of TUFT1 were increased in primary RCC tissue and RCC cell lines. TUFT1 overexpression in RCC cells resulted in enhanced cell proliferation and migration while knockdown of TUFT1 by contrast decreased the growth and migration of the RCC cells, indicating TUFT1 expression is involved in RCC cell growth and migration. The involvement of TUFT1 in the epithelial-mesenchymal transition (EMT) of RCC cells was also determined by measuring the expression of EMT-related markers. Our data showed that TUFT1 overexpression promoted RCC cell EMT progression while knockdown of TUFT1 suppressed such process. Further signaling pathway inhibition assay revealed that TUFT1-induced RCC cell growth, migration and EMT was significantly suppressed by PI3K inhibitor, but not JNK or MEK inhibitors. In addition, TUFT1 overexpression enhanced the AKT phosphorylation, a key member of the PI3K signaling pathway, while PI3K inhibitor suppressed such process. Taken together, our study showed that TUFT1 expression was elevated in RCC and such elevation promoted the proliferation, migration and EMT of RCC cells in vitro, through PI3K/AKT signaling pathway. The findings of our current study imply that TUFT1 is involved in RCC tumorigenesis, and it may serve as a biomarker for RCC diagnosis and a potential target for RCC treatment.

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

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.

Effect of TUTF1 expression on the proliferation, apoptosis and prognosis of hepatocellular carcinoma cells / 中华肝脏病杂志

Objective@#To study the relationship between the expressions of tuftelin 1 (TUFT1) and the clinicopathological features of hepatocellular carcinoma and its effect on proliferation and apoptosis, and to explore the relationship between TUFT1 with the development of hepatocellular carcinoma.@*Methods@#Immunohistochemistry was used to detect the expression of TUFT1 in 98 cases of hepatocellular carcinoma and 30 cases of adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of TUFT1 in HCC cell line. The expression of TUFT1 in SMMC-7221 cell lines was down-regulated by lentiviral vector. Cell proliferation assay, clonogenic assay, cell apoptosis assay and cell cycle assay were used to detect proliferation, apoptosis, and cell cycle changes of hepatocarcinoma cells after TUFT1-down-regulation. Statistics were performed using the χ2 test and the t-test.@*Results@#Among the 98 cases of hepatocellular carcinoma, 65 cases (66.33%) were positive for TUFT1, and in 30 cases of adjacent normal tissues, 6 cases (16.67%) were positive for TUFT1, and the difference was statistically significant (χ 2 = 19.956, P < 0.05). The expression of TUFT1 in HCC tissues was related to tumor size, tumor stage, recurrence and metastasis (χ2 = 6.214, 8.066, 14.400, P < 0.05). After lentiviral vector mediated downregulation of TUFT1 expression in SMMC -7221 cells, the cell proliferation rate [(18.62% ± 0.15%) vs. (67.91% ± 0.62%), P < 0.05], clonality [(8.10% ± 0.80%) vs. (50.80% ± 1.60%), P < 0.05] and G1 phase cells [(36.71% ± 0.69%) vs. (44.65% ± 0.73%), P < 0.05] were significantly decreased, whereas the G2 phase cells [ (15.44% ± 0.53%) vs. (22.31% ± 0.20%), P < 0.05] and the rate of apoptosis [(3.45% ± 0.18%) vs. (5.45% ± 0.06%), P < 0.05] was significantly increased compared with the control group of HCC cells, and the differences were statistically significant.@*Conclusion@#The expression of TUFT1 is highly expressed in hepatocellular carcinoma tissues. Furthermore, the expression of TUFT1 promotes HCC cell proliferation, inhibits the apoptosis, and is poor prognostic factor of hepatocellular carcinoma.

[Effect of TUTF1 expression on the proliferation, apoptosis and prognosis of hepatocellular carcinoma cells].

Objective: To study the relationship between the expressions of tuftelin 1 (TUFT1) and the clinicopathological features of hepatocellular carcinoma and its effect on proliferation and apoptosis, and to explore the relationship between TUFT1 with the development of hepatocellular carcinoma. Methods: Immunohistochemistry was used to detect the expression of TUFT1 in 98 cases of hepatocellular carcinoma and 30 cases of adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of TUFT1 in HCC cell line. The expression of TUFT1 in SMMC-7221 cell lines was down-regulated by lentiviral vector. Cell proliferation assay, clonogenic assay, cell apoptosis assay and cell cycle assay were used to detect proliferation, apoptosis, and cell cycle changes of hepatocarcinoma cells after TUFT1-down-regulation. Statistics were performed using the χ2 test and the t-test. Results: Among the 98 cases of hepatocellular carcinoma, 65 cases (66.33%) were positive for TUFT1, and in 30 cases of adjacent normal tissues, 6 cases (16.67%) were positive for TUFT1, and the difference was statistically significant (χ (2) = 19.956, P < 0.05). The expression of TUFT1 in HCC tissues was related to tumor size, tumor stage, recurrence and metastasis (χ(2) = 6.214, 8.066, 14.400, P < 0.05). After lentiviral vector mediated downregulation of TUFT1 expression in SMMC -7221 cells, the cell proliferation rate [(18.62% ± 0.15%) vs. (67.91% ± 0.62%), P < 0.05], clonality [(8.10% ± 0.80%) vs. (50.80% ± 1.60%), P < 0.05] and G1 phase cells [(36.71% ± 0.69%) vs. (44.65% ± 0.73%), P < 0.05] were significantly decreased, whereas the G2 phase cells [ (15.44% ± 0.53%) vs. (22.31% ± 0.20%), P < 0.05] and the rate of apoptosis [(3.45% ± 0.18%) vs. (5.45% ± 0.06%), P < 0.05] was significantly increased compared with the control group of HCC cells, and the differences were statistically significant. Conclusion: The expression of TUFT1 is highly expressed in hepatocellular carcinoma tissues. Furthermore, the expression of TUFT1 promotes HCC cell proliferation, inhibits the apoptosis, and is poor prognostic factor of hepatocellular carcinoma.