MiR-30c-5p loss-induced PELI1 accumulation regulates cell proliferation and migration via activating PI3K/AKT pathway in papillary thyroid carcinoma.

BACKGROUND: The aberrant expression of E3 ubiquitin ligase Pellino-1 (PELI1) contributes to several human cancer development and progression. However, its expression patterns and functional importance in papillary thyroid cancer (PTC) remains unknown. METHODS: PELI1 expression profiles in PTC tissues were obtained and analyzed through the starBase v3.0 analysis. Real-time PCR, Immunohistochemical assays (IHC) and Western blot were used to investigate the mRNA and protein levels of PELI1 in PTC. The effects of PELI1 on PTC cell progression were evaluated through CCK-8, colony formation, Transwell, and Wound healing assay in vitro, and a PTC xenograft mouse model in vivo. The downstream target signal of PELI1 in PTC was analyzed by using Kyoto encyclopedia of genes and genomes (KEGG), and bioinformatics tools were used to identify potential miRNAs targeting PELI1. Human umbilical cord mesenchymal stem cells were modified by miR-30c-5p and the miR-30c-5p containing extracellular vesicles were collected (miR-30c-5p-EVs) by ultra-high-speed centrifugation method. Then, the effects of miR-30c-5p-EVs on PELI1 expression and PTC progression were evaluated both in vitro and in vivo. RESULTS: Both mRNA and protein expression of PELI1 were widely increased in PTC tissues, and overexpression of PELI1 was positively correlated with bigger tumor size and lymph node metastases. PELI1 promoted PTC cell proliferation and migration in vitro. While, PELI1 silencing significantly suppressed PTC growth in vivo accompanied with reduced expression of Ki-67 and matrix metallopeptidase 2 (MMP-2). Mechanistically, PI3K-AKT pathway was identified as the downstream target of PELI1, and mediated the functional influence of PELI1 in PTC cells. Moreover, we found that the expression of miR-30c-5p was inversely correlated with PELI1 in PTC samples and further confirmed that miR-30c-5p was a tumor-suppressive miRNA that directly targeted PELI1 to inhibit PTC cell proliferation and migration. Furthermore, we showed that miR-30c-5p-EVs could effectively downregulate PELI1 expression and suppress the PTC cell growth in vitro and in vivo. CONCLUSION: This study not only supported the first evidence that miR-30c-5p loss-induced PELI1 accumulation facilitated cell proliferation and migration by activating the PI3K-AKT pathway in PTC but also provided novel insights into PTC therapy based on miR-carrying-hUCMSC-EVs.

Thyroid antibody status exerts insignificant effect on lymph node metastasis of thyroid cancer.

BACKGROUND: To investigate whether high thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are associated with increased risk of lymph node metastasis (LNM) of thyroid cancer. METHODS: Data of 2,352 patients who committed thyroidectomy from January 2018 to December 2018 at our institution were retrospectively reviewed. Of which, 806 patients diagnosed with thyroid cancer with available data of both TPOAb and TgAb were finally included, and were divided into four groups: (I) TPOAb-/TgAb- (control, n=493), (II) TPOAb+/TgAb- (n=96), (III) TPOAb-/TgAb+ (n=104), and (IV) TPOAb+/TgAb+ (n=113). The demographic and clinicopathological data were analyzed. RESULTS: Compared to control, significantly less extrathyroidal invasions were identified in TPOAb+ and/or TgAb+ patients (P<0.05), while no significant differences for tumor size, multifocality, or central/lateral neck LNM rate were found for TPOAb+ and/or TgAb+ groups (all P>0.05). Compared to control, significantly more lymph nodes were removed during neck dissection (P<0.05), but there were no significant differences for the number or size of lymph nodes involved (all P>0.05) for TPOAb+ and/or TgAb+ patients. TPOAb+ and/or TgAb+ were not identified as risk factors or protect factors of LNM of thyroid cancer in Logistic regression analyses. CONCLUSIONS: In the present study, we demonstrated that anti-thyroid peroxidase and thyroglobulin antibodies are not associated with increased risk of lymph node metastasis of thyroid cancer.

Comparison Of The Effects Of Focus Harmonic Scalpel And Conventional Haemostasis On Parathyroid Function In Thyroid Surgery.

BACKGROUND: Protection of parathyroid is very important in thyroid surgery. Our aim was to compare the effect of Focus Harmonic Scalpel and Conventional Haemostasis on parathyroid function in thyroid surgery. METHODS: To analyse the clinical data of patients in our hospital from November 2011-December 2015 retrospectively. Operations have been performed with Focus Harmonic Scalpel in thyroid surgery since May 2013. Seventy-four patients with nodular goitre constituted Harmonic Scalpel group and Conventional Haemostasis group, and so did 139 patients with thyroid papillary carcinoma. Clinical data were compared such as age, gender, thyroid volume, operation procedure, preoperative parathyroid hormone and serum calcium concentration between the two groups. The differences between the two groups were observed in serum calcium concentration, parathyroid hormone concentration, incidence of transient hypocalcaemia and hypoparathyroidism after operation. RESULTS: The preoperative data showed no significant difference between Harmonic Scalpel group and Conventional Haemostasis group. No significant difference existed in postoperative clinic data at six a.m. the first day after operation between the two groups for patients with nodular goitre. The incidence of transient hypoparathyroidism and hypocalcaemia in Harmonic Scalpel group were less than that in Conventional Haemostasis group in thyroid surgery. Significant differences existed in the mean of serum calcium concentration and incidence of transient hypocalcaemia between the two groups for thyroid papillary carcinoma statistically. CONCLUSION: Focus Harmonic Scalpel has certain advantages than conventional Haemostasis in protecting parathyroid glands, reducing the incidence of transient hypoparathyroidism and hypocalcaemia in thyroid surgery, especially for patients with thyroid cancer.

Histone preconditioning protects against obstructive jaundice-induced liver injury in rats.

A major consequence of obstructive jaundice (OJ) in clinical practice is the development of severe liver injury, and at present, no effective treatments have been developed to protect against it. Preconditioning with damage-associated molecular pattern (DAMP) molecules has been demonstrated to protect multiple organs from injury, and histones have been recently identified as DAMP molecules. The aim of the present study was to investigate the protective effect of histone preconditioning against OJ-induced liver injury in rats and the involvement of Toll-like receptors. Rats were administered histone proteins (200 µg/kg; 1 ml) or physiological saline (1 ml) intraperitoneally 24 h prior to being subjected to bile duct ligation (BDL). The serum levels of liver enzymes and bilirubin, as well as the histopathology were analyzed. The mRNA expression of interleukin-6 (IL-6) in the liver tissue was analyzed using quantitative polymerase chain reaction. BDL in the control group caused severe OJ-induced liver injury, as indicated by the significantly elevated levels of liver enzymes and mRNA levels of IL-6, and confirmed by histopathological alterations. However, histone preconditioning significantly ameliorated the OJ-induced liver injury caused by BDL, as shown by an improvement in the levels of liver enzymes, a suppression of IL-6 production, as well as histopathological alterations. Therefore, these results suggested that histone preconditioning is able to protect against OJ-induced liver injury in rats.