CircNRIP1 Exerts Oncogenic Functions in Papillary Thyroid Carcinoma by Sponging miR-653-5p and Regulating PBX3 Expression

Abstract

Background. Circular RNA circ_0004771 (termed circNRIP1) was identified by RNA-Seq previously and was elevated in papillary thyroid carcinoma (PTC) tissues. A series of studies also showed that circNRIP1 was upregulated in some tumors and could promote the malignant progression of tumors. This research intended to focus on the role of circNRIP1 in PTC progression and explore the mechanisms underlying circNRIP1 functions. Methods. RT-PCR or western blot determined circNRIP1, miR-653-5p, and pre-B-cell leukemia homeobox 3 (PBX3) expression. EdU, CCK-8, Tunel, and transwell assays determined cell proliferation, apoptosis, invasion, and migration, respectively. Luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull down assays clarified the target relation between miR-653-5p and circNRIP1 or PBX3. Xenograft models were applied to explore the role of circNRIP1 in vivo. Results. circNRIP1 significantly increased in PTC tissues and PTC cell lines than that in normal ones. Higher circNRIP1 expression was associated with the TNM stage and poorer overall survival. circNRIP1 knockdown attenuated the malignant progression of PTC, specifically by inhibiting proliferation and invasion/migration and promoting apoptosis. circNRIP1 was a miR-653-5p sponge; miR-653-5p knockdown reversed the suppressive role of circNRIP1 silence in PTC progression. PBX3, a target of miR-653-5p, was positively medicated through circNRIP1 via competitively sponging miR-653-5p. Knockdown of circNRIP1 attenuated the PTC tumor progression via miR-653-5p/PBX3 axis. Conclusion. Silencing of circNRIP1 suppressed PTC development via miR-653-5p elevation and PBX3 reduction, providing a novel perspective for understanding PTC pathogenesis.

Circular RNA nuclear receptor interacting protein 1 promoted biliary tract cancer epithelial‐mesenchymal transition and stemness by regulating the miR‐515‐5p/AKT2 axis and PI3K/AKT/mTOR signaling pathway

“…Meng et al identified that circ_PTK2 promoted EMT‐mediated tumor metastasis and gemcitabine resistance in bladder cancer via modulate PABPC1and SETDB1 expression 36 . Long‐standing evidence suggested that circ_NRIP1 acted as oncogenes in various cancers including cervical cancer, ovarian cancer, nasopharyngeal carcinoma, papillary thyroid carcinoma, osteosarcoma, and so on 37–41 . However, the specific roles of circ_NRIP1 in BTC remain unclear.…”

“…36 Long-standing evidence suggested that circ_NRIP1 acted as oncogenes in various cancers including cervical cancer, ovarian cancer, nasopharyngeal carcinoma, papillary thyroid carcinoma, osteosarcoma, and so on. [37][38][39][40][41] However, the specific roles of circ_NRIP1 in BTC remain unclear. Consequently, we decided to investigate whether circ_NRIP1 expedited BTC progression (Figure 8).…”

CircRNA_0044556 regulates paclitaxel resistance in triple-negative breast cancer by targeting miR-665

“…As a circRNA encoded by COL1A1, previous studies have shown that circRNA_0044556 plays a vital role in the occurrence and development of tumors, including colorectal cancer [20,21], gastric cancer [22] and TNBC [12]. The in nite malignant proliferation of tumor cells and inhibition of apoptosis are the core factors in tumor development and change [23,24]. Therefore, we performed a series of experiments in this study.…”

Emerging roles of circular RNAs in regulating the hallmarks of thyroid cancer

“…These proteins regulate the mitochondrial outer membrane permeability and release apoptotic signaling proteins through multiple signaling pathways. In thyroid cancers, 10 circRNAs have been reported to inhibit cancer cell apoptosis via ceRNA mechanisms [ 60 – 68 ]. For instance, circ_0057209 upregulates STK4 by acting as a miR-183 sponge to activate the Hippo pathway.…”