Oncogenic pseudogene DUXAP10 knockdown suppresses proliferation and invasion and induces apoptosis of papillary thyroid carcinoma cells by inhibition of Akt/mTOR pathway

Abstract

Pseudogenes, another novel group of non‐coding segments without protein‐coding capacity, are closely associated with tumourigenesis and cancer progression. Double homeoboxA pseudogene 10 (DUXAP10) is reported to be robustly expressed in thyroid carcinoma. However, the functional role and underlying mechanism of DUXAP10 in papillary thyroid carcinoma (PTC) progression remain undefined. DUXAP10 expression in PTC cells was detected by qRT‐PCR. Cell proliferation and invasion were determined using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and Transwell invasion assay, respectively. Apoptosis was evaluated using flow cytometry. Protein expression of matrix metalloproteinase (MMP)‐2, MMP‐9, protein kinase B (Akt), phosphorylated Akt, mammalian target of rapamycin (mTOR), and phosphorylated mTOR was examined by western blot. Results showed that DUXAP10 was significantly overexpressed in PTC cells compared with normal thyroid follicular epithelium cells. DUXAP10 silencing suppressed cell proliferation and invasive ability, reduced the expression of MMP‐2 and MMP‐9, and increased apoptotic rate and caspase‐3 activity in PTC cells. Additionally, the Akt/mTOR pathway was inhibited following DUXAP10 knockdown in PTC cells. Activation of the Akt/mTOR pathway by 740Y‐P and MHY1485 attenuated DUXAP10 knockdown‐induced proliferation reduction, invasion suppression and apoptosis in PTC cells. In conclusion, DUXAP10 knockdown suppressed proliferation and invasion and induced apoptosis in PTC cells at least partially by inhibition of the Akt/mTOR pathway.

The LncRNA DUXAP10 Could Function as a Promising Oncogene in Human Cancer

“…By modulating the Wnt/β-catenin and PI3K/Akt signaling pathways, DUXAP10 has been demonstrated to influence the invasion and migration of HCC (Han et al, 2019) SMMC-7721 and HepG2 cells through the regulation of EMT. A previous study of PTC also demonstrated that DUXAP10 was involved in increasing cell invasion and migration and regulating EMT via activation of the Akt/mTOR (Li et al, 2020) pathway. Additionally, DUXAP10 was found to play a crucial role in GC (Xu et al, 2018) cell invasiveness and migration by interacting with the RNA-binding protein HuR and subsequently stabilizing β-catenin mRNA.…”

“…PTC is the most common type of thyroid carcinoma (Li et al, 2018;Hu et al, 2019;Wang et al, 2021a). DUXAP10 was first confirmed by Li et al (2020) to be highly expressed in PTC tissues and TPC-1, BCPAP, K1, and IHH-4 cells compared with adjacent normal thyroid tissues. In addition, DUXAP10 has been demonstrated to contribute to protumorigenic effects by promoting BCPAP and K1 (Li et al, 2020) cell proliferation and invasion in addition to inhibiting cell apoptosis.…”

“…In PTC (Li et al, 2020), there was experimental evidence that DUXAP10 restrained cell apoptosis via inactivation of Caspase-3, in turn resulting in the promotion of proliferative ability in BCPAP and K1 cells. Moreover, DUXAP10 was found to facilitate cell proliferation and inhibit the apoptosis of CML (Yao et al, 2018) K652 and KG-1 cells by inhibiting PTEN expression.…”

“…Increasing studies have demonstrated that DUXAP10 is involved in the tumorigenesis and development of tumors through the modulation of diverse cellular processes, comprising cell colony formation, cell cycle progression, cell proliferation, apoptosis, metastasis, and even CSC-like properties. Moreover, numerous molecular mechanism experiments have confirmed that DUXAP10 plays a tumor promoter role by regulating key target gene activity and affecting multiple important signaling pathways, making it a possible molecular factor that can be used as a therapeutic target in HCC (Han et al, 2019;Sun et al, 2019), NSCLC (Wei et al, 2017), glioma (Wu et al, 2021), RCC (Chen et al, 2020), PTC (Li et al, 2020), OC (Zhang et al, 2018), GC (Xu et al, 2018), PC (Lian et al, 2018), BC (Lv et al, 2018), CRC (Lian et al, 2017) and ESCC (Wang et al, 2018). Therefore, a further indepth understanding of the pro-oncogenic mechanisms of DUXAP10 for cancer treatment is needed.…”

Pseudogene legumain promotes thyroid carcinoma progression via the microRNA‑495/autophagy pathway

“…Studies have demonstrated that the pseudogenes BRAF and DUXAP10 are dysregulated in thyroid carcinoma ( 10 , 32 ). Consistent with these findings, the current study indicated that LGMN was upregulated in thyroid carcinoma, and that this increase in expression was associated with a poorer outcome.…”