Background/Aims: DNA HRR pathway and BER pathway play vital roles in differentiated thyroid cancer (DTC) development, thus we supposed that polymorphisms of XRCC1, XRCC2, XRCC3 DNA repair genes are associated with thyroid cancer risk and progression. Methods: We searched the NCBI database for relevant literatures to determine eight SNPs to be included in our study (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539). Results: SNP of rs25487 was linked with a 53% decrease in DTC risk (OR: 0.47; 95%CI: 0.268-0.82; P = 0.01). For SNP of rs1799782, the homozygous TT genotype indicated a statistically significant 2-fold increased risk of DTC (OR: 2.09; 95%CI: 1.27-3.43; P < 0.001) after multivariate adjustment. For SNP of rs861539, the homozygous TT genotype suggested statistically significant 3-fold increased risk of DTC (OR: 3.02; 95%CI: 1.68-5.42; P < 0.001). No significant association between the other five SNPs and DTC risk. Besides that, female was linked with 47% increase in DTC risk (OR: 1.47; 95%CI: 1.062-2.04; P = 0.02) after multivariate adjustment. Similar results for most of the SNPs were obtained from subgroup analysis by different histological types of DTC. Haplotype analysis revealed that AGC and GGT haplotypes of XRCC1 polymorphisms were associated with DTC. Moreover, results from gene-gene interaction showed that XRCC1-rs25487, XRCC1- rs1799782 and XRCC3- rs861539 variants jointly contributed to a specifically increased risk of DTC, with the combination variant of rs1799782-CT heterozygote and rs861539-TT homozygote exhibiting a higher 3.66-fold risk of DTC (OR: 3.66; 95% CI: 1.476-9.091, P = 0.005). Conclusion: Polymorphisms of XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539), may play a critical role in DTC development and progression. Furthermore, XRCC1 variant can interact with XRCC3 variant to significantly increase DTC susceptibility. Identifying these genetic risk markers could provide evidence for exploring the insight pathogenesis and develop novel therapeutic strategies for DTC.

Certain long non-coding (lnc)RNAs have been reported to serve important roles in the genesis and progression of thyroid cancer (TC). Recent studies have demonstrated that the expression of lncRNA H19 is upregulated in TC tissues; however, knowledge of the associated molecular mechanisms is limited. Therefore, the present study aimed to clarify the roles of H19 in TC. The mRNA expression of lncRNA H19 in TC tissues was determined using reverse transcription-quantitative polymerase chain reaction analysis, and the effects of H19 knockdown on cell viability and apoptosis in vitro were assessed using MTT and flow cytometric assays, respectively. Finally, the signaling pathways involved in the effects of H19 were examined. The results indicated that H19 was upregulated in TC tissues. Silencing of H19 inhibited the cell viability and promoted apoptosis of FTC-133 and TPC-1 TC cells, accompanied by an increased expression of B-cell lymphoma 2 (Bcl-2)-associated X protein and caspase 3, and repressed expression of Bcl-2. The results of western blot analysis suggested that the levels of phosphorylated phosphoinositide-3 kinase (PI3K) and phosphorylated AKT were attenuated by H19 silencing. These results suggest that lncRNA H19 exerts an oncogenic function in TC, in part through the PI3K/AKT pathway.

Accumulating evidence has demonstrated that thioredoxin interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors and functions as a tumor suppressor. However, the association between TXNIP and clear cell renal cell carcinoma (CCRCC) has not yet been fully elucidated. The aim of the present study was to evaluate the role of TXNIP in CCRCC using The Cancer Genome Atlas (TCGA) database. The RNA sequencing data and corresponding clinical data were collected from TCGA database. The association between TXNIP and patient clinicopathological characteristics was analyzed using analysis of variance and logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess the association between TXNIP and overall survival. Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. TXNIP expression was identified to be decreased in CCRCC tissues compared with normal tissues. The decreased expression of TXNIP in CCRCC was significantly associated with clinical stage [OR=0.509 for III vs. I (P=0.002); OR=0.527 for IV vs. I (P=0.012)], T stage [OR=0.552 for T3 vs. T1 (P=0.002)] and grade [OR=0.261 for G4 vs. G1 (P=0.027)]. Kaplan-Meier survival analysis indicated that cases of CCRCC with low TXNIP expression were associated with poorer prognoses compared with those with a high expression level (P=0.002). Univariate and multivariate Cox analyses indicated that TXNIP was an independent prognostic factor in CCRCC. GSEA revealed that 6 pathways exhibited significant differential enrichment in the TXNIP high-expression phenotype, including the WNT signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositol signaling system, the transforming growth factor-β (TGF-β) signaling pathway, autophagy and the Janus kinase (JAK)-STAT signaling pathway. Taken together, the results of the present study indicate that TXNIP expression may be a potential prognostic marker for patients with CCRCC. In addition, the WNT signaling pathway, MAPK signaling pathway, phosphatidylinositol signaling system, TGF-β signaling pathway, autophagy and the JAK-STAT signaling pathway may be the crucial pathways regulated by TXNIP in CCRCC.

The aim of the present study was to investigate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) in tissues of papillary thyroid cancer (PTC) in comparison with the expression in adjacent normal tissues. The expression of STAT3, pSTAT3, fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor-C (VEGF-C) was examined in tissues of 42 cases of PTC and the adjacent normal tissues of 20 of the 42 PTC cases using immunohistochemistry and western blotting. The association between the expression levels and the clinicopathological features was analyzed. The expression of STAT3, pSTAT3, FGF2 and VEGF-C in the PTC tissues (76.2, 42.9, 81.0 and 73.8%, respectively) was significantly higher than that in the normal tissues (P<0.05). In the PTC tissues, the expression of STAT3 was linearly correlated with the levels of pSTAT3 and VEGF-C (P<0.05). In conclusion, STAT3 and pSTAT3 are significantly upregulated in PTC tissues, and may potentially be used as markers to screen for PTC with lymph node metastasis.

Aim: To explore the roles of lncRNA MALAT1 and SHOC2 in breast cancer, and the potential connections to chemotherapy resistance in breast cancer. Materials & methods: Paclitaxel-resistant breast cancer cells were induced by gradually increasing intermittent doses. Bioinformatic analyses were performed to predict the regulated miRNAs of MALAT1. Results: High expressions of MALAT1 and SHOC2 contribute to paclitaxel resistance in breast cancer cells. MALAT1 sponges miR-497-5p enhance SHOC2 expression in paclitaxel-resistant breast cancer cells and contribute to paclitaxel resistance in breast cancer cells. Conclusion: Patients with high expression of MALAT1 and SHOC2 have a poorer response to paclitaxel. Upregulation of miR-497-5p could improve the treatment response to paclitaxel in patients with breast cancer by inhibiting MALAT1 and SHOC2.