Long non‐coding RNA NR2F1‐AS1 promoted proliferation and migration yet suppressed apoptosis of thyroid cancer cells through regulating miRNA‐338‐3p/CCND1axis

Abstract

Thyroid cancer (TC) is a prevalent endocrine malignant cancer whose pathogenic mechanism remains unclear. The aim of the study was to investigate the roles of long non‐coding RNA (lncRNA) NR2F1‐AS1/miRNA‐338‐3P/CCND1 axis in TC progression. Differentially expressed lncRNAs and mRNAs in TC tissues were screened out and visualized by R program. Relative expression of NR2F1‐AS1, miRNA‐338‐3p and cyclin D1 (CCND1) was determined by quantitative real time polymerase chain reaction. In addition, Western blot analysis was adopted for evaluation of protein expression of CCND1. Targeted relationships between NR2F1‐AS1 and miRNA‐338‐3p, as well as miRNA‐338‐3p and CCND1 were predicted using bioinformatics analysis and validated by dual‐luciferase reporter gene assay. Besides, tumour xenograft assay was adopted for verification of the role of NR2F1‐AS1 in TC in vivo. NR2F1‐AS1 and CCND1 were overexpressed, whereas miRNA‐338‐3p was down‐regulated in TC tissues and cell lines. Down‐regulation of NR2F1‐AS1 and CCND1 suppressed proliferation and migration of TC cells yet greatly enhanced cell apoptotic rate. Silence of NR2F1‐AS1 significantly suppressed TC tumorigenesis in vivo. NR2F1‐AS1 sponged miRNA‐338‐3p to up‐regulate CCND1 expression to promote TC progression. Our study demonstrated that up‐regulation of NR2F1‐AS1 accelerated TC progression through regulating miRNA‐338‐3P/CCND1 axis.

LncRNA FGD5‐AS1 can be predicted as therapeutic target in oral cancer

“…LncRNAs have been reported to be aberrantly expressed in many diseases, including cancer, and plays a vital role in tumor growth and progression . Furthermore, lncRNAs have been discovered to be participated in various biological and pathological activities, such as cell growth, apoptosis, invasion, and migration …”

“…[5][6][7][8] Furthermore, lncRNAs have been discovered to be participated in various biological and pathological activities, such as cell growth, apoptosis, invasion, and migration. [9][10][11] MicroRNAs (miRNAs) are another type of non-coding RNAs characterized by short length. It can interact with the 3′ untranslated regions (UTR) of the target genes via its microRNA response elements (MREs), which will silence the expression of downstream target genes.…”

Long non‑coding RNA NR2F1‑AS1 facilitates the osteosarcoma cell malignant phenotype via the miR‑485‑5p/miR‑218‑5p/BIRC5 axis

“…NR2F1-AS1, a recently discovered lncRNA, has been found to enhance esophageal squamous cell carcinoma (ESCC) progression by regulating the Hedgehog signaling pathway (12). NR2F1-AS1 has also been reported to regulate the microRNA (miR)-338-3p/cyclin D1 axis to promote thyroid cancer progression (13). In papillary thyroid carcinoma, NR2F1-AS1 has been confirmed to exacerbate cell proliferation by regulating the miR-423-5p/SRY-box transcription factor (SOX)12 signaling pathway (14).…”

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

“…Recently, CCND1 has been identified as a key gene by integrated bioinformatics analysis [85]. Nevertheless, the role of CCND1 in thyroid tumorigenesis has been poorly investigated, except for recent papers showing CCND1 as a direct target of deregulated miRNAs and long non-coding RNAs [86][87][88]. We identified cyclin D1 as vulnerability for TC cells, as its siRNA-mediated inhibition causes consistent growth reduction of different thyroid tumor cell lines, but not normal ones.…”