NEAT1_2 functions as a competing endogenous RNA to regulate ATAD2 expression by sponging microRNA-106b-5p in papillary thyroid cancer

Abstract

Nuclear paraspeckle assembly transcript 1 (NEAT1), a long non-coding RNA (lncRNA), is a core structural component of paraspeckles and is essential for paraspeckle formation. NEAT1 comprises two different isoforms: NEAT1_1 (3.7 kb) and NEAT1_2 (23 kb). Recently, NEAT1 has been shown to have oncogenic roles and to facilitate tumorigenesis in various human cancers. However, the function of NEAT1 in papillary thyroid cancer (PTC) is not well understood. The relative expression levels of NEAT1_2, ATPase family AAA domain-containing protein 2 (ATAD2), and microRNA-106b-5p (miR-106b-5p) were assessed via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Four PTC cell lines were used to detect the relative expression of NEAT1_2. The effects of NEAT1_2 on PTC cells were studied by RNA interference approaches in vitro. The effects of NEAT1_2 on downstream proteins were detected by western blotting. The underlying mechanism was clarified by a rescue experiment, and three dual-luciferase reporter assays. NEAT1_2 expression was markedly increased in PTC tissues and the PTC cell lines (K1 and TPC1). The relative expression level of NEAT1_2 was positively associated with TNM stage and tumor size. NEAT1_2 knockdown led to a significant inhibition of growth and metastasis, and induced apoptosis in PTC cells. Knockdown of NEAT1_2 significantly inhibited malignant biological behavior by downregulating the oncogene ATAD2. In addition, NEAT1_2 could act as a competing endogenous RNA to regulate the expression of ATAD2 through downregulating miR-106b-5p. Taken together, our results indicated that NEAT1_2 is overexpressed in PTC. NEAT1_2 could function as a competing endogenous RNA to regulate ATAD2 expression by sponging miR-106b-5p in PTC. Targeting NEAT1_2 could be a promising therapeutic strategy for patients with PTC.

LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR‐101‐3p in gastric cancer

“…20,23 There are also reports that the long non-coding RNA NEAT1-2 adsorbs miR-106b-5p through the sponge, thereby up-regulating the expression of the ATAD2 gene in PTC to promote tumorigenesis and progression. 24 LncRNA-HOXA11-AS adsorbs miR-1297 through ceRNA mechanism to promote the proliferation and metastasis of GC cells. 25 Therefore, in order to clarify the mechanism by which LINC01303 promotes the development of F I G U R E 4 LINC01303/miR-101-3p/EZH2 signalling regulates GC progression.…”

miR‐106b‐5p promotes aggressive progression of hepatocellular carcinoma via targeting RUNX3

“…Growing evidence show that miRNAs may be potential therapeutic targets for their roles in regulating either oncogenes or tumor suppressor genes. Recent studies have revealed that miR‐106b‐5p may play an oncogenic role in various cancer types by promoting malignant cell viability and invasion . For example, Lu et al revealed that miR‐106b‐5p could mediate the constitutive activation of Wnt/β‐catenin signaling, and promote renal cell carcinoma aggressiveness and stem cell‐like phenotypes; Wei et al indicated that miR‐106b‐5p overexpression promoted proliferation and inhibited apoptosis by downregulating BTG3 expression in vitro, as well as xenograft tumor formation in vivo; Liu et al found that miR‐106b‐5p could boost glioma tumorigensis by targeting multiple tumor suppressor genes, including RBL1, RBL2, and CASP8; Yu et al demonstrated that miR‐106b‐5p enhanced the sensitivity of nonsmall‐cell lung cancer cell line A549/DDP to cisplatin by targeting the expression of PKD2.…”

“…It belongs to the miR‐106b seed family which has been indicated to be closely associated with cell proliferation, cell cycle, and cell motility . Accumulating studies have reported that miR‐106b‐5p plays an important role in various cancers through diverse mechanisms . Particularly, Shi et al found that the expression of miR‐106b‐5p was higher in HCC tissues and cell lines than that in nontumor tissues and hepatocytes, respectively.…”

Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

“…For example, NEAT1_2 expression was significantly upregulated in papillary thyroid cancer tissues, and increased NEAT1_2 expression was positively related to patients TNM stage and tumor size; downregulation of NEAT1_2 resulted in significant inhibition of cell growth and metastasis by acting as a competing endogenous RNA for miR‐106b‐5p to regulate ATAD2 expression 28. In addition, lncRNA HCP5 is overexpressed in papillary thyroid cancer and promotes proliferation, invasiveness, and angiogenic ability of papillary thyroid cancer cells through functioning as a sponge for miR‐22‐3p, miR‐186‐5p, and miR‐216a‐5p and antagonizing their repression of ST6GAL2 29.…”