TNRC6C-AS1 Promotes Thyroid Cancer Progression by Upregulating LPAR5 via miR-513c-5p.

BACKGROUND: Considering the combined role of long non-coding RNA (lncRNAs)-microRNA (miRNA)-mRNA in tumorigenesis, the purpose of this study was to investigate how TNRC6C-AS1 regulates the expression of lysophosphatidic acid receptor 5 (LPAR5) by modulating miR-513c-5p, thus influencing the progression of thyroid cancer (THCA). METHODS: qRT-PCR and Western blotting were performed to detect the expression levels of TNRC6C-AS1, miR-513c-5p, and LPAR5 in THCA tissues and cell lines. The viability, proliferation, migration, and invasion were assessed using CCK-8, BrdU, wound healing, and transwell migration assays, respectively. Dual-luciferase reporter assay, RIP assay, and RNA pull-down assay were used to evaluate the relationship between TNRC6C-AS1, miR-513c-5p, and LPAR5. RESULTS: TNRC6C-AS1 was highly expressed in THCA tissues, and knockout of TNRC6C-AS1 reduced the viability, proliferation, migration, and invasion of THCA cells. TNRC6C-AS1 competitively adsorbed miR-513c-5p. In addition, the biological function of TNRC6C-AS1 was blocked by knocking down the thyroid cell line TNRC6C-AS1 with miR-513c-5p inhibitor transfection. LPAR5 is the target gene for miR-513c-5p, which has the ability to eliminate the influence of miR-513c-5p on THCA cells. CONCLUSION: The TNRC6C-AS1/miR-513c-5p/LPAR5 axis is a novel signaling pathway that modulates THCA progression and may be a potential target for cancer therapy.

YY1-induced up-regulation of FOXE1 is negatively regulated by miR-129-5p and contributes to the progression of papillary thyroid microcarcinoma.

BACKGROUND: Papillary thyroid microcarcinoma (PTM) belongs to papillary carcinomas whose length is about 1.0 cm. According to previous studies, FOXE1 is a transcription factor involved in the progression of papillary thyroid carcinoma (PTC). However, its detailed upstream mechanism remains unknown in PTM. OBJECTIVE: Our study aimed at detecting and verifying the up-regulation of FOXE1 in PTM cell lines. METHODS: FXOE1 expression was detected in PTM and normal cells through RT-qPCR. Loss-of-function experiments were conducted to identify the effect of silenced FOXE1 on cell proliferation, apoptosis, migration and invasion. Mechanism experiments were carried out to explore the upstream molecular mechanism of FOXE1. RESULTS: Knockdown of FOXE1 could lead to the inhibition on cell proliferation, migration and invasion while positively regulating cell apoptosis. Importantly, Yin-Yang-1 (YY1) could boost the transcription of FOXE1, thereby upregulating FOXE1. Also, the binding potential of miR-129-5p to FOXE1 was identified in PTM cells and MiR-129-5p could target FOXE1. In addition, the cellular processes in PTM were hindered with the increase of miR-129-5p expression level. CONCLUSION: Our research suggested that the up-regulation of FOXE1 is regulated by YY1 and miR-129-5p, which may contribute to PTM progression.

The role of vascular epithelial growth factor receptor-tyrosine kinase inhibitors in the treatment of advanced breast cancer: a meta-analysis of 12 randomized controlled trials.

AIM: To perform a systematic review and meta-analysis of randomized controlled trials to determine the efficacy and toxicity of approved vascular epithelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) in advanced breast cancer. METHODS: A comprehensive literature search for studies published up to August 2013 was performed. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3 or 4 adverse event (AEs). The pooled hazard ratio (HR) or relative risk (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. RESULTS: Twelve randomized controlled trials involved 3256 patients were ultimately identified. The intention to treatment (ITT) analysis demonstrated that VEGFR-TKI therapy significantly improved ORR (RR 1.14, 95% CI: 1.03-1.28, p = 0.016), but it did not translate into benefits in PFS (HR 0.99, 95% CI: 0.81-1.22, p = 0.93) and OS (HR 1.11, 95% CI 0.99-1.24, p = 0.084) when compared to non-VEGFR-TKI therapy. Additionally, a higher incidence of grade 3 or 4 anemia, neutropenia, thrombocytopenia, diarrhea, hand-foot syndrome and fatigue was observed in VEGFR-TKI-based therapy. CONCLUSIONS: The VEGFR-TKI-based therapy offered a significant improvement in ORR in patients with advanced breast cancer but did not benefit PFS and OS. With present available data from randomized clinical trials, we were still unable to clearly set the role of VEGFR-TKIs in the treatment of metastatic breast cancer (MBC).