The long noncoding RNA NORAD enhances the TGF‐β pathway to promote hepatocellular carcinoma progression by targeting miR‐202‐5p

Abstract

Hepatocellular carcinoma (HCC) is one of the most fatal cancers with common features of invasion and metastasis. Recent evidence indicate that the long noncoding RNA NORAD is a potential oncogene and is significantly upregulated in several cancers. However, the general biological role and clinical value of NORAD in HCC remains unknown. Here, NORAD expression was measured in 29 paired tumor and paratumor tissues via quantitative real‐time polymerase chain reaction (qPCR). The effects of NORAD on HCC cell malignant potential were investigated via NORAD overexpression and knockdown both in vitro and in vivo. The mechanism of competitive endogenous RNAs (ceRNAs) was acquired and identified by bioinformatics analyses and luciferase assays. Moreover, the impact of NORAD level on the transforming growth factor β (TGF‐β) pathway was further determined by qPCR. We found that HCC tissues had a high level of NORAD compared with the paratumor tissues, and NORAD upregulation was associated with the shorter overall survival of patients with HCC. Furthermore, NORAD overexpression was demonstrated to promote HCC cell migration and invasion. Mechanically, NORAD might function as a ceRNA to regulate miR‐202‐5p, which served as a tumor‐suppressing microRNA via the TGF‐β pathway. We address that NORAD has a tumor‐promoting effect in HCC and describes a novel mechanism whereby NORAD regulates the TGF‐β pathway as a ceRNA of Homo sapiens (hsa)‐miR‐202‐5p.

LBX2-AS1/miR-219a-2-3p/FUS/LBX2 positive feedback loop contributes to the proliferation of gastric cancer

“…*P < 0.05, **P < 0.01 lncRNAs can serve as sponges of microRNAs (miRNAs) targeting downstream genes. For instances, LINC00665 boosts the progression of lung adenocarcinoma by regulating AKR1B10-ERK signaling through sponging miR-98 [34]; lncRNA NORAD activate the TGF-β pathway to facilitate hepatocellular carcinoma progression by miR-202-5p [35]; STAT3-induced upregulation of lncRNA MEG3 regulates the growth of cardiac hypertrophy through miR-361-5p/ HDAC9 axis [36]. Hence, 23 predicted target miRNAs of LBX2-AS1 obtained from starBase were analyzed by qRT-PCR.…”

NORAD regulates epithelial‑mesenchymal transition of non‑small cell lung cancer cells via miR‑422a

“…Moreover, developing effective strategies to improve the prognosis of NSCLC remains a challenge. NORAD is an important lncRNA that serves a key role in cancer cell migration and invasion ( 19 , 20 ). lncRNAs have critical functions during cancer progression ( 21 , 22 ).…”

ACTA2‐AS1 suppresses lung adenocarcinoma progression via sequestering miR‐378a‐3p and miR‐4428 to elevate SOX7 expression

“…By modulation of the miR‐199a/MRP1 axis, LINC00518 contributes to the drug resistance of breast cancer cells (Chang, Hu, Zhou, & Zhang, 2018). lncRNA NORAD helps the transforming growth factor‐β pathway to cause the progression of hepatocellular carcinoma by targeting miR‐202‐5p (Yang et al, 2019). In the present study, it was a spot that the cytoplasmic part of A549 and PC‐9 cells contained much more ACTA2‐AS1 expression than the nuclear part, implying that ACTA2‐AS1 might engage in the posttranscriptional regulation.…”