Proactive exploration of inferior parathyroid gland using a novel meticulous thyrothymic ligament dissection technique.

INTRODUCTION: The inferior parathyroid gland (IPTG) is widely distributed; effective techniques for its safe exploration and protection during thyroid surgery have not been documented. The thyrothymic ligament (TTL) is a connective tissue located between the thymic tongue and thyroid. This study aims to introduce a novel meticulous thyrothymic ligament dissection technique and assess its role in proactive exploration and situ preservation of IPTG. MATERIALS AND METHODS: 737 patients undergoing initial thyroid surgery between 2017 and 2021 in the Department of General Surgery of the First Affiliated Hospital of Nanjing Medical University were retrospectively recruited for this clinical study. In 391 of the recruited patients, the TTL was dissected, and the number and location of IPTG were recorded. Among them, 214 patients underwent total/near-total thyroidectomy (TT) plus central neck dissection (CND) were assigned to the observation group. The control group included 346 consecutive patients who underwent conventional TT plus CND. After 1:1 propensity score matching, each group contained 206 patients. The incidence of postoperative hypoparathyroidism was recorded. RESULTS: Among the 391 patients, 596 sides were dissected, out of which 436 sides (73.2%) had TTL, and approximately 90.1% of IPTG were located and identified. A statistically significant difference in incidence of temporary (27.7 vs. 49.0%, P < 0.001) and permanent hypoparathyroidism (0 vs. 8.2%, P = 0.047) was noted between the observation group and the control group. CONCLUSION: The meticulous thyrothymic ligament dissection technique helps to protect IPTG in situ and reduce the incidence of postoperative hypoparathyroidism.

Long noncoding RNA FER1L4 promotes the malignant processes of papillary thyroid cancer by targeting the miR-612/ Cadherin 4 axis.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in various cancers. However, the functional roles of most lncRNA in papillary thyroid cancer (PTC) are not detailly understood. This study aims to investigate the biological function and molecular mechanism of lncRNA Fer-1 like family member 4 (FER1L4) in PTC. METHODS: The expression of FER1L4 in PTC was determined via operating quantitative real-time PCR assays. Meanwhile, the clinical significance of FER1L4 in patients with PTC was described. The biological functions of FER1L4 on PTC cells were evaluated by gain and loss of function experiments. Moreover, animal experiments were performed to reveal the effect on tumor growth. Subcellular distribution of FER1L4 was determined by fluorescence in situ hybridization and subcellular localization assays. Luciferase reporter assay and RNA immunoprecipitation assay were applied to define the relationship between FER1L4, miR-612, and Cadherin 4 (CDH4). RESULTS: Upregulated expression of FER1L4 in PTC tissues was positively correlated with lymph node metastasis (P = 0.020), extrathyroidal extension (P = 0.013) and advanced TNM stages (P = 0.013). In addition, knockdown of FER1L4 suppressed PTC cell proliferation, migration, and invasion, whereas ectopic expression of FER1L4 inversely promoted these processes. Mechanistically, FER1L4 could competitively bind with miR-612 to prevent the degradation of its target gene CDH4. This condition was further confirmed in the rescue assays. CONCLUSIONS: This study first demonstrates FER1L4 plays an oncogenic role in PTC via a FER1L4-miR-612-CDH4 axis and may provide new therapeutic and diagnostic targets for PTC.

The direct miR-874-3p-target FAM84A promotes tumor development in papillary thyroid cancer.

With the improvement in diagnostic technology, the incidence of thyroid cancer (TC) is on the rise. Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer; therefore, it is important to explore some valuable molecular targets to improve the treatment and prognosis of PTC. Studies have shown that family with sequence similarity 84, member A (FAM84A) is involved in the development of various tumors. However, the role of FAM84A in PTC remains unknown. Herein, we explored the biological function and specific molecular mechanism of FAM84A in PTC. Results indicated that FAM84A was upregulated in PTC tissues and cells. In addition, patients with higher FAM84A expression tended to possess larger tumor size, higher lymph node metastasis rate, and advanced TNM stage. Further studies indicated that downregulation of FAM84A could inhibit the development of PTC in vitro and in vivo by repressing the epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling pathway. Moreover, FAM84A was confirmed to be negatively regulated by tumor suppressor miR-874-3p. In conclusion, our findings suggest that FAM84A may act as a potential diagnostic and therapeutic target for PTC.

Long noncoding RNA ZFAS1 promotes progression of papillary thyroid carcinoma by sponging miR-590-3p and upregulating HMGA2 expression.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy, papillary thyroid carcinoma (PTC) is the main form of thyroid cancer. The long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is highly expressed in various cancer tissues and it has been shown to function as a tumor promoter in various cellular processes. However, the role of ZFAS1 in PTC is not well understood currently. Thus, this study aimed to explore the potential roles of ZFAS1 in the development and progression of PTC. MATERIAL AND METHODS: PTC tissues (n=80) and noncancerous tissues were collected. Gain- and loss-of-function assays were performed to determine the effect of ZFAS1 on proliferation in K-1 and TPC-1 cells. The ZFAS1/mir-590-3P/HMGA2 aixs were analysed in PTC cell lines. RESULTS: We found that the expression of ZFAS1 was increased in PTC tissues and four PTC cell lines (B-CPAP, IHH-4, TPC-1, and K-1). The gain- and loss-of-function assays showed that overexpressing ZFAS1 promoted cell proliferation and inhibited cell apoptosis in PTC cells in vitro. We demonstrated that knockdown of ZFAS1 inhibits tumor growth and upregulation of ZFAS1 promotes tumor growth in vivo. Bioinformatics analysis revealed that miR-590-3p targeted the 3'-UTR of ZFAS1. The double luciferase reporter and RNA-binding protein immunoprecipitation assay demonstrated that miR-590-3p is a target of ZFAS1. Rescue experiments confirmed that miR-590-3p could reverse the effect of ZFAS1 on PTC cells. Moreover, we identified high mobility group AT-hook 2 (HMGA2) to be a downstream target of miR-590-3p and ZFAS1 which activates HMGA2 expression by sponging to miR-590-3p. CONCLUSION: High ZFAS1 expression level was associated with the progression of PTC, and ZFAS1 contributed to PTC progression via miR-590-3p/HMGA2 regulatory aixs. Therefore, ZFAS1 might be a potential therapeutic target for PTC intervention.

Long noncoding RNA ABHD11-AS1 functions as a competing endogenous RNA to regulate papillary thyroid cancer progression by miR-199a-5p/SLC1A5 axis.

With the increasing incidence of papillary thyroid cancer (PTC), more attention has been paid to exploring the mechanism of PTC initiation and progression. In addition, ectopic expression of long noncoding RNAs (lncRNAs) is reported to play a pivotal role in multiple human cancers. Based on these findings, we examined lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) expression and its clinical significance, biological function and mechanism in PTC. First, we analyzed thyroid ABHD11-AS1 expression in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then, qRT-PCR was applied to detect the expression in paired PTC tissues and adjacent normal tissues, as well as in PTC cell lines (TPC-1 and K-1) and a normal thyroid follicular epithelium cell line (Nthy-ori3-1). In addition, we validated the relationship between ABHD11-AS1 expression and clinicopathological features by the Pearson X2 test. The oncogenic role of ABHD11-AS1 and its regulation of miR-199a-5p in PTC were examined by biological assays. Finally, bioinformatics analysis and mechanism assays were used to elucidate the underlying mechanism. We found that ABHD11-AS1 was remarkably overexpressed in PTC, and high expression was related to tumor size, lymph node metastasis, extrathyroidal extension and advanced TNM stage. Moreover, ABHD11-AS1 enhanced the abilities of cell proliferation, migration, and invasion, inhibited apoptosis in vitro, promoted tumorigenesis in vivo via sponging miR-199a-5p and then induced SLC1A5 activation. In addition, rescue assays were performed to confirm the ABHD11-AS1/miR-199a-5p/SLC1A5 axis. Taken together, the data show that ABHD11-AS1 acts as a competing endogenous RNA (ceRNA) to exert malignant properties in PTC through the miR-199a-5p/SLC1A5 axis. Therefore, our study may shed light on PTC diagnosis and therapies.