miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1.

Our previous study has demonstrated that miR-455-5p was a tumor suppressor in colorectal cancer (CRC). This study aimed to investigate the role of miR-455-5p in 5-fluorouracil (5-Fu) in CRC. The expression of miR-455-5p, PIK3R1, and DEPDC1 was analyzed in HT-29 cells after treatment with different concentrations (0, 0.5, 2.5, and 12.5 µM) of 5-Fu. The effects of miR-455-5p on cell proliferation and apoptosis were analyzed by CCK-8 and flow cytometry. PIK3R1 and DEPDC1 were overexpressed to measure the mechanism of miR-455-5p on 5-Fu sensitivity. And the direct binding between miR-455-5p and DEPDC1 was detected by a dual-luciferase reporter assay. We found that miR-455-5p decreased, while PIK3R1 and DEPDC1 increased after 5-Fu treatment. miR-455-5p mimic significantly suppressed cell viability and elevated cell apoptosis in 5-Fu-treated HT-29 cells, whereas miR-455-5p inhibitor showed the opposite effects. Overexpression of PIK3R1 and DEPDC1 could attenuate the effects of miR-455-5p mimic on the viability and apoptosis of 5-Fu-treated cells. miR-455-5p could directly bind to DEPDC1 in HT-29 cells. In conclusion, miR-455-5p enhanced 5-Fu sensitivity by targeting PIK3R1 and DEPDC1 in CRC. This study provides a novel role of miR-455-5p in CRC and restoring miR-455-5p might be a therapeutic strategy to enhance chemosensitivity to 5-Fu.

Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis.

BACKGROUND: The role of circular RNA (circRNA) in papillary thyroid cancer (PTC) is largely unknown. This study aims to determine the function and mechanism of circPRMT5 in the regulation of PTC development. METHODS: PTC tissues and cell lines were used to determine circPRMT5 expression via quantitative real-time polymerase chain reaction. Small interfering RNA (siRNA) was utilized to knock down circPRMT5. Proliferation was analyzed through CCK8 and colony formation assays. Transwell assay was performed to determine cell migration and invasion. Luciferase assay and RIP assay were carried out to analyze the interaction between circPRMT5 and miR-30c. RESULTS: CircPRMT5 expression was upregulated in PTC tissues and cell lines. And circPRMT5 level was positively linked with advanced stage and lymph node metastasis. CircPRMT5 knockdown inhibited proliferation, migration and invasion while inducing apoptosis. CircPRMT5 worked as a competing endogenous RNA for miR-30c. By inhibiting miR-30c, circPRMT5 promoted the expression of E2F3. CONCLUSION: Our findings demonstrate that circPRMT5 acts as an oncogenic circRNA to promote PTC progression via regulating miR-30c/E2F3 axis.

LncRNA PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 axis.

Study has shown that long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was elevated in colorectal cancer tissues and cells, and the proliferation and metastasis of colorectal cancer cells were reduced after its downregulation. The tumor-suppressive role of microRNA-150-5p (miR-150-5p) has been shown in colorectal cancer. In this study, the association between PART1 and miR-150-5p in colorectal cancer was analyzed. Results revealed an increase of PART1, but a decrease of miR-150-5p in 56 colorectal cancer tissues. And there was a strong negative correlation between levels of PART1 and miR-150-5p in these cancer samples. Also, compared with 10 healthy controls, the level of PART1 was increased, whereas miR-150-5p expression was diminished in the serum of 10 colorectal cancer patients. Cell proliferation and migration, along with epithelial-mesenchymal transition, was promoted by PART1 overexpression. However, this lncRNA mitigated apoptosis of colorectal cancer cells. Whereas miR-150-5p mimic abrogated these effects caused by PART1 overexpression. The influences of PART1 knockdown on the above malignant characteristics of colorectal cancer cells were contrary to its overexpression. miR-150-5p inhibitor ablated the effects induced by PART1 knockdown. In xenograft mouse models, silencing of PART1 decreased tumor volume and weight. Our data supported that lncRNA PART1 may regulate leucine-rich α-2-glycoprotein-1 (LRG1) expression through a competing interaction mechanism that hindering miR-150-5p function. In conclusion, PART1 facilitates the malignant progression of colorectal cancer via miR-150-5p/LRG1 pathway. The study further clarified the molecular mechanism of PART1 in colorectal cancer. This study may provide a new approach to diagnose and treat colorectal cancer.

Defining a New Tumor Dimension in Staging of Papillary Thyroid Carcinoma.

BACKGROUND: Cervical lymph node metastasis is a vital factor associated with local recurrence in papillary thyroid carcinoma (PTC). Tumor size is used in the staging of PTC because it represents the tumor load. This study compared two methods of tumor size assessment to predict tumor behavior in the relationship between size and cervical node involvement for patients with PTC. METHODS: The study enrolled 1084 patients who underwent initial thyroid surgery and had a pathologic diagnosis of PTC between 2012 and 2014 at The Second Affiliated Hospital Zhejiang University School of Medicine. Cervical lymph node metastasis (LNM) risk was analyzed according to the clinicopathologic features. For each patient with multifocal disease, two tumor size estimates were used: (1) the dominant focus size and (2) the aggregate size, calculated as the sum of the maximal diameters of all tumor foci. RESULTS: Of the 1084 patients, 294 (27.1%) had multifocal cancer lesions, and 49% of these patients had cervical LNM, compared with 38.1% who had unifocal disease (P = 0.001). The use of aggregate dimension significantly increased the tumor size and reclassified significant numbers of multifocal PTCs to a more advanced T stage. This aggregate dimension took account of all tumor foci and predicted LNM risk at a proportion identical with that for size-matched, unifocal tumors. CONCLUSION: Multifocality together with aggregate tumor size is a more accurate predictor of node status and, by inference, tumor behavior in the relationship between tumor size and cervical node involvement.

Implementation of Intraoperative Neuromonitoring for Transoral Endoscopic Thyroid Surgery: A Preliminary Report.

BACKGROUND: Transoral endoscopic approach is the natural orifice surgery applied in thyroidectomy to achieve an excellent cosmetic result. Recurrent laryngeal nerve (RLN) injury is the most common complication and little advancement was achieved in the previous clinical studies of transoral thyroid surgery. Herein, we introduced the method of intraoperative neuromonitoring (IONM) for transoral endoscopic thyroid surgery. MATERIALS AND METHODS: Patients with thyroid carcinoma received transoral endoscopic thyroid surgery through vestibular approach (TOETVA) for thyroidectomy and central node dissection (CND). IONM was implemented to identify whether the RLN benefited from oral tracheal intubation. The laryngeal electromyography (EMG) response, operation time, number of CND, drainage volume, hospital duration, surgical complications, and cosmetic results were evaluated. RESULTS: From August to October 2015, 10 cases were performed with TOETVA and IONM. All EMG responses were recorded intraoperatively, and no case experienced transient or permanent RLN palsy. The operation time ranged from 130 to 215 minutes in ipsilateral lobectomy with CND, whereas bilateral lobectomy with ipsilateral CND lasted 345 minutes. The number of CNDs ranged from three to eight. The average time of drainage extubation and discharge was 4 days (3-5 days) postoperatively. All patients were satisfied with the cosmetic results, and no infection was observed at lip wound or in the anterior neck region. CONCLUSION: IONM system implemented in transoral thyroid surgery was feasible and serviceable in preventing RLN injury. The method of TOETVA shows promise for thyroidectomy with CND due its ideal cosmetic results.

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms.

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trß was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.

Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report.

Primary thyroid paraganglioma (TP) is an uncommon tumor, and in rare cases, this disease tends to mimic medullary thyroid carcinoma (MTC). The present study reports a rare case of primary TP mimicking thyroid carcinoma, accompanied by hyperthyroidism. A 30-year-old female presented with an anterior cervical mass. Pre-operative radiological studies and operative frozen section analysis indicated an atypical MTC. Primary TP was finally diagnosed by pathology and immunohistochemical staining. Laboratory examinations (thyroid hormones tests) and Tc99m emission computed tomography revealed hyperthyroidism. Gene analysis of TP-associated gene mutations was negative. Surgical resection was performed as a curative approach and there is currently no metastasis after 36 months of follow-up. Surgeons must be aware of this disease in order to ensure a correct diagnosis and to prevent them from performing unnecessary procedures. The current study presents a case of primary TP mimicking MTC, discusses the radiographic results and histological characteristics, and provides a review of the associated literature.