MicroRNA‑874 inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells by directly targeting paired box 6

Abstract

Studies have demonstrated that a number of microRNAs (miRNAs) are dysregulated in pancreatic ductal adenocarcinoma (PDAC), and alterations in their expression may affect the onset and progression of PDAC. Therefore, the expression patterns, biological functions and associated molecular mechanisms of miRNAs in PDAC should be elucidated for the development of novel therapeutic methods. Previous studies reported significant miRNA‑874 (miR‑874) dysregulation in multiple types of human cancer. However, the expression pattern, possible roles and underlying mechanisms of miR‑874 in PDAC remain to be elucidated. This study evaluated miR‑874 expression in PDAC and examined its biological functions and underlying mechanism of action in PDAC progression. miR‑874 expression was downregulated in PDAC tissues and cell lines. Functional experiments demonstrated that upregulation of miR‑874 inhibited cell proliferation and invasion in PDAC. Additionally, paired box 6 (PAX6) was predicted as a putative target of miR‑874 using bioinformatics analysis. Further experiments demonstrated that PAX6 may be the direct target gene of miR‑874 in PDAC. PAX6 knockdown exhibited similar inhibitory effects to miR‑874 overexpression in PDAC cells. In addition, restored PAX6 expression may reverse the suppressive roles of miR‑874 overexpression in PDAC cells. The results demonstrated that miR‑874 may serve tumor suppressive roles in PDAC by directly targeting PAX6. Therefore, miR‑874 may exhibit potential applications for treatment of patients with PDAC.

MicroRNA-664 targets paired box protein 6 to inhibit the oncogenicity of pancreatic ductal adenocarcinoma

“…PAX6 was also overexpressed in PDAC. The high expression of PAX6 is closely related with PDAC progression and development, and it has been described to affect a multitude of biological behaviors, including cell growth, cycle status, differentiation and metastasis (28,29).…”

“…3A, PAX6 harbors a potential miR-664 binding site. PAX6 was selected for further investigation as this well-known oncogene has been well documented to be involved in the genesis and development of PDAC (28,29). A luciferase reporter assay was applied to determine whether the 3'-UTR of PAX6 is directly targeted by miR-664 in PDAC cells.…”

The Role and Expression of Angiogenesis-Related miRNAs in Gastric Cancer

“…Similarly, miR-874 has been recognized as playing a tumor suppressor role in non-small cell lung cancer (NSCLC) both in vitro and in vivo [104]. Similar results have been achieved in pancreatic cancer [105].…”

miR-874: An Important Regulator in Human Diseases

“…As shown in Table 1 , miR-874 is downregulated in at least 22 human malignancies, such as colorectal cancer (CRC) ( Huang et al, 2020a ; Yu et al, 2020 ; Que et al, 2017 ; Zhao and Dong, 2016 ; Han et al, 2016 ; Wang et al, 2021 ; Zhang et al, 2021c ), gastric cancer (GC) ( Huang et al, 2018 ; Sun et al, 2020 ; Yuan et al, 2020 ; Liu et al, 2017 ; Zhang et al, 2015 ; Jiang et al, 2014 ), hepatocellular carcinoma (HCC) ( Zhang et al, 2018b ; Jiang et al, 2017 ; Leong et al, 2017 ; Song et al, 2016 ), esophageal squamous cell carcinoma (ESCC) ( Yuan et al, 2018 ), pancreatic ductal adenocarcinoma (PDAC) ( Diao et al, 2018 ), non-small cell lung cancer (NSCLC) ( Bu et al, 2020 ; Yang et al, 2017 ; Ahmad et al, 2015 ; Kesanakurti et al, 2013 ; Wang et al, 2020b ), osteosarcoma (OS) ( Tang et al, 2018 ; Liu et al, 2020 ; Dong et al, 2016 ; Ghosh et al, 2017 ), epithelial ovarian cancer (EOC) ( Xia et al, 2018 ) cervical cancer (CC) ( Liao et al, 2018 ; Liu et al, 2021a ), retinoblastoma (RB) ( Zhang et al, 2018a ; Wang et al, 2020a ), prostate cancer (PCa) ( Pashaei et al, 2017 ) maxillary sinus squamous cell carcinoma (MSCC) ( Nohata et al, 2011 ), breast cancer (BC) ( Li et al, 2020 ; Zhang et al, 2017 ; Wang et al, 2014 ), triple-negative breast cancer (TNBC) ( Wu et al, 2020 ), rhabdomyosarcoma (RMS) ( Shang et al, 2019 ), papillary thyroid carcinoma (PTC) ( Ding et al, 2021 ), endometrial cancer ( Witek et al, 2021 ), cholangiocarcinoma ( Pan et al, 2021 ), glioma ( Li et al, 2021a ), myeloma (MM) ( Tian et al, 2021 ), head and neck squamous cell carcinoma (HNSCC) ( Nohata et al, 2013 ) and acute myeloid leukemia (AML) ( Zhang et al, 2021a ).…”

“…In patients of HCC, OS, or RMS, decreased expression of miR-874 is associated with tumor size, vascular infiltration, lymph node metastasis, tumor-node-metastasis (TNM) staging, clinical staging, and tumor differentiation ( Dong et al, 2016 ; Zhang et al, 2018b ; Shang et al, 2019 ). Subsequent cell function experiments revealed the tumor suppressor effects of miR-874, including inhibition of proliferation, invasion, metastasis, and promotion of apoptosis ( Diao et al, 2018 ) ( Table 3 ).…”