Downregulation of long noncoding RNA CASC15 inhibits progression, migration and invasion of papillary thyroid cancer.

Introduction: Thyroid cancers are the most common malignancy of the endocrine system. Increasing evidence has suggested potential roles for cancer susceptibility candidate 15 (CASC15) in thyroid cancer. Papillary thyroid cancer (PTC) accounts for 80% of thyroid cancer, posing a great threat to public health. The present study aims to investigate the potential roles of CASC15 in PTC. Material and methods: PTC tissues were obtained from patients diagnosed with PTC at the Second Hospital of Hebei Medical University from October 2016 to January 2018. qRT-PCR was performed to examine the mRNA levels of CASC15, Bcl-2/BAX, E-cadherin, caspase-3, and PI3K/AKT. Western blotting was applied to determine the protein levels of PI3K/AKT, CASC15, E-cadherin, BAX, Bcl-2 and caspase-3. CCK-8 assays were used to determine the viability of BCPAP and K1 cancer cells. Wound healing and transwell assays were conducted to evaluate the migration and invasion abilities of BCPAP and K1 cells. Results: The results showed that CASC15 was upregulated in thyroid cancer tissues. Moreover, CASC15 in BCPAP and K1 was decreased by CASC15 siRNA. The progression, migration and invasion of BCPAP cells were significantly decreased after transfection with CASC15 siRNA, which was consistent with that in K1 cells. Furthermore, CASC15 siRNA treatment decreased the level of Bcl-2, and PI3K/AKT, and increased the expression of E-cadherin, BAX, and caspase-3. Conclusions: Downregulated CASC15 inhibited the proliferation, migration and invasion of thyroid cancer. Therefore, CASC15 may be an oncogene in thyroid cancer and may serve as a target marker for the treatment of thyroid cancer.

Expression and Clinical Significance of Thyroid-stimulating hormone receptor in the Subtypes of Papillary thyroid carcinomas.

Objective: To investigate the expression of TSH receptors (TSHR) in various subtypes of Papillary thyroid carcinomas (PTC) by immunohistochemistry. Methods: Retrospective analyses were carried out to the clinical data of 108 PTC patients randomly admitted into the Department of Thyroidthyroid surgery thyroid surgery and Breast Surgery, The Second Hospital of Hebei Medical University from March 2020 to December 2020. The archived paraffin blocks of the 108 cases as well as 18 contiguous normal thyroid tissues (control group) were taken from the Department of Pathology of The Second Hospital of Hebei Medical University. The pathological types of all PTC tissues were detected and the expression of TSHR was determined. Results: TSHR expression was 86.11% positive in PTC tissues; with 85.00% positive in classical group; with 75.86% positive in micro group; with 84.61% positive in follicular group; with 83.33% positive in oncocytic group; with 50.00% positive in invasive group. TSHR expression was 100% in normal thyroid tissues. So TSHR expression in normal thyroid tissues is significantly higher than that in PTC; TSHR expression in microcarcinoma is stronger than in the other subtypes; there is no significant difference among the other subtypes. Conclusions: TSH suppression works better on microcarcinoma than on the other subtypes. And the effects on non-invasive subtypes are better than on invasive subtypes.

Risk factor score for the prediction of central compartment lymph node metastasis in papillary thyroid carcinoma and its clinical significance.

Objective: To establish the criteria for a risk factor score (RFS) for predicting the probability of central compartment lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) and to explore the clinical significance of the RFS. Methods: The data of 412 patients with PTC who underwent surgical resection between May 2013 and July 2016 were retrospectively analysed and divided into two groups: a central LNM group and a non-central LNM group. In each group, the frequency of six risk factors was documented: sex, age, tumour size, extracapsular spread (ECS), tumour multifocality, and tumour location. The maximum likelihood method of discriminant analysis was adopted to calculate patient scores for the six risk indicators. In addition, the data of 104 patients with PTC admitted between July 2016 and December 2016 were prospectively analysed using this method and these six risk factors. A higher score represented one certain possibility that was the more appropriate for one patient. Results: In the retrospective group, the result was as follows: 129 patients with positive (+) lymph nodes in the central compartment and 168 patients with negative (-) lymph nodes in the central compartment, which was in line with the actual results. In the prospective group, there were 28 patients with positive lymph nodes in the central compartment and 48 patients with negative lymph nodes in the central compartment. The coincidence rates using the RFS were 71.9% for the retrospective group and 73.1% for the prospective group. Conclusion: By simple and quantitative analyses of the presence of central LNM, the RFS is of great significance when choosing surgical approaches and postoperative individual-based treatment plans, as well as when determining the prognosis of central compartment LNM in patients with PTC.

lncRNA MALAT1 regulates the resistance of breast cancer cells to paclitaxel via the miR-497-5p/SHOC2 axis.

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.

Utility and significance of clinical risk factor scoring model in predicting central compartment lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC).

OBJECTIVES: To establish and discuss the significance of a clinical risk factor scoring model in predicting central compartment lymph node metastasis (CLNM) (level VI) in patients with papillary thyroid cancer (PTC). METHODS: A retrospective analysis was performed on 412 patients who underwent surgical treatment for PTC who were admitted to the Second Hospital of Hebei Medical University between July 2016 and May 2017, with the patients being divided into a CLNM group and a non-metastasis (NM) group. Risk factors such as sex, age, tumor diameter, capsular invasion, multifocality, and tumor location were recorded for scoring via maximum likelihood estimation (MLE)-based discriminant analysis. The scoring model was used for prospective analysis of CLNM in another 104 patients. Besides, the discriminant function that was developed using the risk factors based on the retrospective data derived from the 412 patients was evaluated by plugging the retrospective data in for specified variables, with a higher score indicating a greater risk of developing CLNM. Clinical diagnosis of CLNM was based on postoperative paraffin section pathology, which was adopted as the criterion to assess discriminative accuracy in the prospective and retrospective groups. RESULTS: The discriminative accuracy of the scoring model was 71.8% in the retrospective group and 72.2% in the prospective group. CONCLUSIONS: The scoring model enables simplified, quantitative analysis of CLNM in PTC patients. The scoring model has clinical significance in that it provides a basis for the choice of operation, personalized postoperative treatment, and prognosis of PTC.

Overexpression of lncRNA CASC2 inhibits the tumorigenesis of thyroid cancer via sponging miR-24-3p.

BACKGROUND: The incidence of thyroid cancer continues to rise all over the world. Thus, it is urgent to find a novel strategy for the treatment of thyroid cancer. Previous reports have confirmed that lncRNA CASC2 is involved in the pathogenesis of thyroid cancer. However, the mechanism by which CASC2 mediates the tumorigenesis of thyroid cancer remains unclear. METHODS: Gene and protein expressions in tissues or cells were detected by q-PCR and Western blot, respectively. Cell proliferation was tested by MTT assay. Flow cytometry was used to test cell apoptosis. Cell migration and invasion in thyroid cancer cells was detected by transwell assay. In addition, the correlation between CASC2 and miR-24-3p were investigated by Targetscan and dual-luciferase reporter assay. Finally, xenograft mice model was established to detect the effect of CASC2 on thyroid cancer in vivo. RESULTS: CASC2 was significantly downregulated in thyroid cancer. Overexpression of CASC2 inhibited the proliferation, migration, and invasion of thyroid cancer cells. In addition, upregulation of CASC2 could inhibit the tumorigenesis of TC via sponging miR-24-3p. Furthermore, overexpression of CASC2 significantly suppressed the growth of thyroid cancer in vivo. CONCLUSION: Overexpression of CCASC2 inhibits the tumorigenesis of thyroid cancer in vitro and in vivo. Thus, CASC2 may serve as a novel target for the treatment of thyroid cancer.

Decreased expression of TXNIP predicts poor prognosis in patients with clear cell renal cell carcinoma.

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-ß (TGF-ß) 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-ß signaling pathway, autophagy and the JAK-STAT signaling pathway may be the crucial pathways regulated by TXNIP in CCRCC.

Long non-coding RNA H19 knockdown inhibits the cell viability and promotes apoptosis of thyroid cancer cells through regulating the PI3K/AKT pathway.

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.

The long non-coding RNA HOTAIR promotes thyroid cancer cell growth, invasion and migration through the miR-1-CCND2 axis.

The purpose of this study was to explore the potential role of HOTAIR in thyroid cancer carcinogenesis. We found that HOTAIR was unregulated in human thyroid cancer and inversely correlated with miR-1. Functional assays indicated HOTAIR regulates miR-1 directly in thyroid cancer cells. We also revealed that HOTAIR promotes the processes of thyroid cancer cell malignancy through regulation of microRNA-1 (miR-1). Furthermore, we showed that HOTAIR could regulate a downstream target of miR-1, CCND2, in a miR-1-mediated manner. In addition, we also proved, using a tumor formation assay in nude mice, that silencing HOTAIR inhibited tumor formation in vivo. Therefore, our study demonstrated that HOTAIR promotes the development and progression of thyroid cancer through inhibition of microRNA-1 and activation of CCND2.

The lncRNA n340790 accelerates carcinogenesis of thyroid cancer by regulating miR-1254.

Long non-coding RNAs (lncRNAs) have been recently reported to be dysregulated and play a critical role in the progression of thyroid cancer. Here, we found that the lncRNA n340790 was highly expressed in human thyroid cancer tissues and was strongly correlated with the clinical characteristics of patients. There was a good prognostic value of n340790 for thyroid cancer. In vitro overexpression of n340790 promoted the development of thyroid cancer, while silencing n340790 inhibited this process. Additionally, n340790 accelerated the growth of thyroid cancer tumor in vivo. Furthermore, we discovered that n340790 could act as an endogenous sponge by directly binding to miR-1254 and downregulating miR-1254 expression. In addition, miR-1254 could inhibit the stimulatory effect of n340790 on the growth and invasion of thyroid cancer cells. In conclusion, n340790 promoted the development process of malignant thyroid cancer by regulating miR-1254, and targeting n340790 may be a promising strategy as a thyroid cancer therapy.

Androgen receptor CAG and GGN repeat length variation contributes more to the tumorigenesis of osteosarcoma.

The androgen receptor (AR) is involved in the differentiation and growth of many cancers. We hypothesized that two microsatellite polymorphic variants, AR (CAG)n and (GGN)n repeats, were also associated with the development of Papillary thyroid cancer (PTC) and Osteosarcoma. In current study, we conducted two case-control studies in a Chinese population to investigate the possible relationship between these two AR repeat polymorphisms and the risk of PTC and Osteosarcoma. The AR CAG repeat length was significantly associated with both risk of PTC and Osteosarcoma. Subjects with shorter AR CAG repeats had a higher risk of developing PTC (OR = 1.47, 95% CI: 1.17-1.85, P = 0.001) and Osteosarcoma (OR = 1.53, 95% CI: 1.19-1.97, P = 9.2 x 10-4). Specifically, shorter GGN repeats also contribute a significant increased risk of Osteosarcoma (OR = 1.35, 95% CI: 1.03-1.77, P = 0.030). Our results contribute to a better understanding of the complex hormone related mechanisms underlying PTC and Osteosarcoma.

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma.

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.

Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer.

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.

Clinical pathologies of breast cancer in the elderly and youths and their prognosis.

OBJECTIVE: To explore the correlation between the clinical pathologies of breast cancer in the elderly and youths as well as their prognosis. METHODS: Two hundred and eighty breast cancer patients were divided into a youth group (<60, n=120) and an elderly group (≥60, n=160) according to the age. Their routine clinical pathological indices and immune indices were observed and determined, and the prognosis was observed after effective treatment. RESULTS: The positive expression rates of p63, CK5/6, CK14 and CK17 in the elderly group were significantly higher than those of the youth group (P<0.05). The tumor-free survival rate of the youth group (95.8%) was significantly higher than that of the elderly group (84.4%) (P<0.05). Multivariate Logistic regression analysis showed that the positive expressions of p63 and estrogen receptor, age, and postoperative chemotherapy were the independent risk factors of tumor-free survival rate (P<0.05). CONCLUSION: The immunohistochemical typing characteristics of the elderly and youths were different, and the prognosis of young patients was better, being correlated with the typing.

[Rare giant salivary gland pleomorphic adenoma on the neck].

The patient has found his neck mass for more than 30 years, and the neck mass has slowly growed into giant tumor. Five days ago, the neck giant mass suddenly burst, hemorrhage and overflow liquid. The giant mass with irregular in shape, surface uneven, skin highly tension and superficial venous engorgement, was seen in left lateral neck. CT scan demonstrates a mixture of solid, cystic and lobulated mass shadow within subcutaneous fat spaces of left lateral neck. Postoperative pathological examination proved that it is salivary gland pleomorphic adenoma.

[Expression of thyroid stimulating hormone receptor in differentiated thyroid carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance. METHODS: Seventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011 were selected as the observation group, and 28 patients with nodular goiter were selected as the control group. Expression of TSH receptor in the two groups were detected by immunohistochemistry. RESULTS: The positive rate of TSH receptor expression in the observation group was 55.4 (41/74), significantly lower than that of the control group (89.3%, 25/28), with a significant difference between the two groups (χ(2) = 10.21, P < 0.05). In the observation group, the positive rate of TSH receptor expression was 75.9% (22/29) in the stage I patients, 47.8% (11/23) in the stage II patients, 38.9%6 (7/18) in the stage III patients, and 25.0% (1/4) in the stage IV patients. Along with the increase of TNM staging, the positive rate of TSH receptor expression was decreased gradually, with a significant difference between them (χ(2) = 8.93, P < 0.05). The positive rate of TSH receptor expression was 53.8% (14/26) in the lymph node metastasis positive group and 56.3% (27/48) in the lymph node metastasis negative groups, with a non-significant difference between them (χ(2) = 0.04, P > 0.05). CONCLUSIONS: Expression of TSH receptors in the patients with differentiated thyroid carcinoma is quite low, and along with the increase of TNM staging, its positive rate is decreasing gradually. Testing the expression of TSH receptor may provide a basis for TSH suppression therapy after thyroid cancer surgery. This TSH suppression therapy should be personalized in order to reduce the side effects and improve their quality of life.