Circ_LDLR promoted the development of papillary thyroid carcinoma via regulating miR-195-5p/LIPH axis.
Circ_LDLR 通过调节 miR-195-5p/LIPH 轴促进甲状腺乳头状癌的发生发展。
- 作者列表："Gui X","Li Y","Zhang X","Su K","Cao W
Background:Emerging studies have demonstrated that circular RNAs (circRNAs) are key regulators for tumorigenesis in cancers, including papillary thyroid carcinoma (PTC). In this study, we aimed to explore the effects of circ_LDLR on PTC. Methods:Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circ_LDLR, miR-195-5p and lipase H (LIPH). RNase R digestion assay and Actinomycin D assay were utilized to analyze the characteristics of circ_LDLR. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay were conducted to evaluate cell proliferation. Western blot assay was used for the determination of protein levels. Flow cytometry analysis was applied to determine cell apoptosis. Transwell assay was performed to determine cell migration and invasion. Dual-luciferase reporter assay was used to verify the associations among circ_LDLR, miR-195-5p and LIPH. The murine xenograft model was constructed to explore the roles of circ_LDLR in vivo. Results:Compared to normal tissues and cells, circ_LDLR was upregulated in PTC tissues and cells. Silencing of circ_LDLR suppressed PTC cell colony formation, proliferation, migration and invasion and promoted apoptosis in vitro and hampered tumor growth in vivo. For mechanism investigation, circ_LDLR could regulate LIPH expression via sponging miR-195-5p. Moreover, miR-195-5p inhibition restored the effects of circ_LDLR knockdown on the malignant behaviors of PTC cells. MiR-195-5p overexpression inhibited PTC cell colony formation, proliferation, migration and invasion and facilitated apoptosis by targeting LIPH. Conclusion:Circ_LDLR knockdown decelerated PTC progression by regulating miR-195-5p/LIPH axis, which might provide a novel therapeutic target for PTC.
背景: 新的研究已经证明环状 rna (circular RNAs，circRNAs) 是包括甲状腺乳头状癌 (PTC) 在内的癌症中肿瘤发生的关键调控因子。在本研究中，我们旨在探讨 circ_LDLR 对 PTC 的影响。 方法: 采用实时荧光定量聚合酶链反应 (qRT-PCR) 检测大鼠血清中 circ_LDLR 、 miR-195-5p 和脂肪酶 H (LIPH) 水平。采用 RNase R 消化试验和放线菌素d 试验分析 circ_LDLR 的特征。进行集落形成实验和 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-h-四唑溴盐 (MTT) 实验以评价细胞增殖。蛋白质印迹试验用于蛋白质水平的测定。应用流式细胞仪分析测定细胞凋亡。进行 Transwell 试验以确定细胞迁移和侵袭。采用双荧光素酶报告基因检测方法验证 circ_LDLR 、 miR-195-5p 和 LIPH 之间的相关性。构建小鼠异种移植模型，探讨 circ_LDLR 在体内的作用。 结果: 与正常组织和细胞相比，circ_LDLR 在 PTC 组织和细胞中表达上调。沉默 circ_LDLR 在体外抑制 PTC 细胞集落形成、增殖、迁移和侵袭，促进细胞凋亡，抑制体内肿瘤生长。对于机制研究，circ_LDLR 可以通过海绵 miR-195-5p 调节 LIPH 的表达。此外，miR-195-5p 抑制恢复了 circ_LDLR 敲除对 PTC 细胞恶性行为的影响。MiR-195-5p 过表达通过靶向 LIPH 抑制 PTC 细胞集落形成、增殖、迁移和侵袭，促进细胞凋亡。 结论: Circ_LDLR 敲除可通过调节 miR-195-5p/LIPH 轴降低 PTC 进展，为 PTC 提供新的治疗靶点。
METHODS:OBJECTIVES:To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS:Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS:Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS:Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma.
METHODS:Background Whether chronic lymphocytic thyroiditis (CLT) influences the risk of development and the progression of papillary thyroid cancer (PTC) remains uncertain. We investigated the effects of CLT on the clinicopathologic features and prognosis of PTC. Methods Two thousand nine hundred twenty-eight consecutive patients with PTC treated between 2009 and 2017 were divided into two groups: one with chronic lymphocytic thyroiditis and one without; 1174 (40%) of the patients had coincident CLT. Results In univariate analysis, CLT correlated positively with small tumor size, frequent extrathyroidal extension, multifocal diseases, and p53 but negatively with central lymph node (LN) metastasis and BRAF mutation. In multivariate analysis, CLT was associated with extrathyroidal extension and multifocal disease; however, it was not a prognostic factor for recurrence even though it was associated with two aggressive factors. Compared with patients with PTC alone, there were more retrieved central LNs in the PTC + CLT group, and these patients also underwent more invasive diagnostic tests such as fine needle aspiration cytology and frozen biopsy of LN. Conclusions The CLT patients with PTC had better behavior features and prognoses than did those with PTC alone despite frequent multifocality and extrathyroidal extension. However, precaution may be necessary to avoid performing invasive diagnostic procedures for lateral LN metastasis and to manage the patients appropriately.
METHODS::PTPN2 is one of the members of the protein Tyrosine Phosphatases (PTPs) family. To explore the promotive effect of upregulated PTPN2 induced by inflammatory response or oxidative stress on the progression of thyroid cancer. PTPN2 level in thyroid cancer tissues and cell lines was detected. Kaplan-Meier method was applied for evaluating the prognostic value of PTPN2 in thyroid cancer patients. After stimulation of inflammatory response (treatment of IFN-γ and TNF-α), or oxidative stress (treatment of H2O2), protein level of PTPN2 in K1 cells was measured by Western blot. Regulatory effects of PTPN2 on EdU-positive staining and Ki-67 positive cell ratio in K1 cells either with H2O2 stimulation or not were determined. PTPN2 was upregulated in thyroid cancer tissues and cell lines. Its level was higher in metastatic thyroid cancer patients than those of non-metastatic ones. High level of PTPN2 predicted worse prognosis of thyroid cancer. Treatment of either IFN-γ or TNF-α upregulated protein level of PTPN2 in K1 cells. Meanwhile, H2O2 stimulation upregulated PTPN2, which was reversed by NAC administration. With the stimulation of increased doses of H2O2, EdU-positive staining and Ki-67 positive cell ratio were dose-dependently elevated. Silence of PTPN2 attenuated proliferative ability and Ki-67 expression in K1 cells either with H2O2 stimulation or not. Inflammatory response or oxidative stress induces upregulation of PTPN2, thus promoting the progression of thyroid cancer.