If NFVPTCs were no longer termed carcinomas, this would affect the rate of malignancy of FNA diagnostic categories. Cytologic and molecular features could aid in identifying NFVPTCs at the time of FNA diagnosis.

VitaminD3 signaling is involved in inhibiting the development and progression of gastric cancer (GC), while the active vitamin D metabolite 1-alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)-mediated gene regulatory mechanisms in GC remain unclear. We found that miR-145 is induced by 1,25(OH)2D3 in a dose- and vitamin D receptor (VDR)-dependent manner in GC cells. Inhibition of miR-145 reverses the antiproliferative effect of 1,25(OH)2D3. Furthermore, miR-145 expression was lower in tumors compared with matched normal samples and correlated with increased the E2F3 transcription factor protein staining. Overexpression of miR-145 inhibited colony formation, cell viability and induced cell arrest in S-phase in GC cells by targeting E2F3 and CDK6. miR-145 inhibition consistently abrogates the 1,25(OH)2D3-mediated suppression of E2F3, CDK6, CDK2 and CCNA2 genes. Altogether, our results indicate that miR-145 mediates the antiproliferative and gene regulatory effects of vitamin D3 in GC cells and might hold promise for prognosis and therapeutic strategies for GC treatment.

In human hepatocellular carcinoma (HCC), aberrant expression of miRNAs correlates with tumor cell proliferation, apoptosis, invasion, and migration by targeting downstream proteins. miR-15b levels are reported increased in HCC tissues; however, they negatively correlate to HCC recurrence. Our aim was to understand the reason for this phenomenon. We used the reverse transcription-polymerase chain reaction (RT-PCR) to measure miR-15b-5p expression in both HCC tissues and HCC cell lines. Our results were consistent with the report. Using bioinformatics and luciferase reporter assays, we identified Rab1A as a novel and direct target of miR-15b-5p. Inhibiting the function of Rab1A with shRab1A also inhibited the growth of HCC cells and induced endoplasmic reticulum stress (ERS) and apoptosis. Similarly, suppressing Rab1A by overexpression of miR-15b-5p also inhibited cell growth and induced ERS and apoptosis. Moreover, re-expression of Rab1A rescued the miR-15b-5p -induced ERS, apoptosis, and growth inhibition in HCC cells. In vivo assays were further performed to testify them. Taken together, our data suggest that miR-15b-5p induces ERS, apoptosis, and growth inhibition by targeting and suppressing Rab1A, acting as a tumor suppressor gene in HCC. This finding suggests a novel relation among Rabs, miRNAs, and apoptosis.

Insulin-like growth factor (IGF) signaling is involved in oral squamous cell carcinoma (OSCC), but IGF-1 receptor (IGF-1R)-mediated intricate regulatory networks among molecular interactions and signalling path ways in OSCC remain unclear. Here, we found that overexpression of IGF-1R and insulin receptor substrate-2 (IRS-2) was negatively associated with histological differentiation. IGF signaling stimulated OSCC cell growth. Conversely, overexpression of let-7b inhibited proliferation and colony formation and triggered S/G2 cell cycle arrest by targeting IGF-1R and IRS-2 through the Akt pathway. Also, the inverse relationship between expression of let-7b and IGF-1R/IRS-2 was confirmed in OSCC tumor xenografts and clinical specimens. Furthermore, by activating ERK1/2, IGF-1R transcriptionally upregulated IRS-2. Our results indicate that let-7b/IGF-1R-mediated crosstalk between IRS-2/Akt and MAPK is involved in OSCC and is a potential therapeutic target for therapy.

Renal neuroendocrine neoplasms are rare, with descriptions of cases limited to individual reports and small series. The natural history of this group of neuroendocrine neoplasms is poorly understood. In this study, we queried the Surveillance, Epidemiology and End Results (SEER) database over a four-decade period where we identified 166 cases of primary renal neuroendocrine neoplasms. We observed a 5-year overall survival of 50%. On multivariate analysis, survival was influenced by stage, histology, and if surgery was performed. We observed that patients managed by operative management had a greater frequency of localized or regional stage disease as well as a greater frequency of neuroendocrine tumor, grade 1 histology; whereas those managed non-operatively tended to have distant disease and histologies of neuroendocrine carcinoma, NOS and small cell neuroendocrine carcinoma. This is the largest description of patients with renal neuroendocrine neoplasms. Increased survival was observed in patients with earlier stage and favorable histologies.

Thyroid cancer is frequently difficult to diagnose due to an overlap of cytologic features between malignant and benign nodules. This overlap leads to unnecessary removal of the thyroid in patients without cancer. While providing some improvement over cytopathologic diagnostics, molecular methods frequently fail to provide a correct diagnosis for thyroid nodules. These approaches are based on the difference between cancer and adjacent thyroid tissue and assume that adjacent tissues are the same as benign nodules. However, in contrast to adjacent tissues, benign thyroid nodules can contain genetic alterations that can be found in cancer. For the development of a new molecular diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid tissues by using genome-wide single-base resolution DNA methylation analysis. The test was validated in a retrospective cohort containing 65 thyroid nodules. By conducting reduced representation bisulfite sequencing in 109 thyroid specimens, we found significant differences between adjacent tissue, benign nodules, and cancer. These tissue-specific signatures are strongly linked to active enhancers and cancer-associated genes. Based on these signatures, we developed a new epigenetic approach for thyroid diagnostics. According to the validation cohort, our test has an estimated specificity of 97% [95% confidence interval (CI), 81-100], sensitivity of 100% (95% CI, 87-100), positive predictive value of 97% (95% CI, 83-100), and negative predictive value of 100% (95% CI, 86-100). These data show that epigenetic testing can provide outstanding diagnostic accuracy for thyroid nodules.

EGR1 regulates the expression of its downstream target genes and may exert different biological effects in different tumours. We found that the expression of EGR1 was increased in gastric cancer (GC), and silencing the expression of EGR1 promoted the apoptosis of GC cells. Moreover, overexpression of EGR1 repressed the apoptosis of GC cells. Bioinformatics analysis showed that EGR1 had binding sites at the upstream promoter region of miR‐195; ChIP assays were applied to determine EGR1 occupancy of the miR‐195 promoter. The RT‐PCR results showed that EGR1 suppressed the expression of miR‐195. The mechanism by which EGR1 acts as a transcriptional repressor is still unclear. Bioinformatics analysis showed that EGR1 may interact with DNMT3L. We confirmed that EGR1 and DNMT3L formed a complex, and EGR1 was an important player in the transcriptional control of miR‐195. Overexpression of miR‐195 inhibited proliferation and promoted apoptosis in GC cells. We found a well‐matched miR‐195 binding site at the AKT3 3′‐UTR. Double luciferase reporter assays showed that AKT3 was a target of miR‐195, and silencing AKT3 repressed cell proliferation and promoted apoptosis. Our results indicated EGR1 may interact with DNMT3L to inhibit the miR‐195‐AKT3 axis and regulate the GC cell apoptosis.

MicroRNAs (miRNAs) are a class of small, non‑coding, endogenous RNAs that are important in tumor cell biological processes as they regulate gene expression. miR-195 has been demonstrated to be a tumor repressor in numerous types of human cancer. However, the mechanism by which miR‑195 suppresses tumor development remains to be elucidated. The aim of this study was to investigate the effect of miR-195 on the biological functions of HepG2 hepatocellular carcinoma (HCC) cells and identify the association between miR-195 and Wnt3a in HCC. miR-195 mRNA expression levels in HCC tissues and cell lines were measured by reverse transcription polymerase chain reaction analysis. miR-195 function was measured with cell proliferation, cell cycle and apoptosis assays following transfection with miR‑195 and anti‑miR‑195 sequences, and the respective controls. Luciferase reporter assay was used to determine whether Wnt3a was a target of miR-195. In addition, Wnt3a expression levels were determined in HCC cells using western blot analysis. The miR-195 expression levels were found to be reduced in HCC tissues and cell lines. miR-195 overexpression resulted in a reduction in cell proliferation. In addition, the overexpression of miR-195 in HCC cells induced G1 phase cell cycle arrest and promoted apoptosis. Furthermore, Wnt3a was demonstrated to be directly targeted by miR-195. These findings suggest that miR-195 is key in regulating cell proliferation, cell cycle and apoptosis through targeting Wnt3a. In addition, overexpression of miR-195 may be a potential therapeutic strategy in the treatment of HCC.