LINC00472 suppressed by ZEB1 regulates the miR‐23a‐3p/FOXO3/BID axis to inhibit the progression of pancreatic cancer

Abstract

The tumour‐suppressive role of LINC00472 has been extensively reported in various human cancers such as lung, colon and ovarian cancers, yet its function in pancreatic cancer remains unidentified. Here, the current research aimed to explore the role and regulatory axis mediated by LINC00472 in the progression of pancreatic cancer. RT‐qPCR was adopted to determine LINC00472 expression in the harvested pancreatic cancer tissues and adjacent normal tissues. Loss‐of‐function and gain‐of‐function experiments were performed to examine the effects of LINC00472 on proliferation and apoptosis in vitro and tumorigenesis in vivo. Immunoblotting was performed to detect the expression of several proliferation and apoptosis‐related proteins. Bioinformatic analysis, dual‐luciferase reporter assay and RNA pull‐down were conducted to profile the relationships between LINC00472 and miR‐23a‐3p, between miR‐23a‐3p and FOXO3 and between FOXO3 and BID. The LINC00472 expression was down‐regulated by ZEB1 in the pancreatic cancer cells and tissues. LINC00472 could competitively bind to miR‐23a‐3p to enhance the expression of FOXO3, which consequently could promote the BID expression, thereby suppressing proliferation and promoting the apoptosis of pancreatic cancer cells. Meanwhile, the inhibitory role of LINC00472 in tumorigenesis was validated in vivo, and the LINC00472‐mediated miR‐23a‐3p/FOXO3/BID axis was also demonstrated in the nude mouse tumour formation model. The study substantiated the antitumour activity of LINC00472 in pancreatic cancer and proposed a regulatory axis in which LINC00472 competitively binds to miR‐23a‐3p to enhance the FOXO3 expression and promote BID expression. Consequently, these findings provide theoretical basis for developing potential targets for the treatment of pancreatic cancer.

Knockdown of hsa_circ_0000729 Inhibits the Tumorigenesis of Non-Small Cell Lung Cancer Through Mediation of miR-1281/FOXO3 Axis

“…FOXO3 is known to be a key regulator in cell growth. 24 In our research, FOXO3 was identified to be the direct target of miR-1281. It has been reported that FOXO3 participate in cell pyroptosis.…”

Long Noncoding RNA 00472: A Novel Biomarker in Human Diseases

“…Thus, it is vital to evaluate the mechanisms of PC progression and to establish novel treatment targets for improving survival outcomes of PC patients. In a previous study, RT-qPCR analysis revealed that LINC00472 levels in pancreatic cancer tissues were suppressed, relative to adjacent normal tissues ( Bi and Wang, 2021 ). Moreover, the study identified correlations between LINC00472 low expressions and TNM stages, lymph node metastases and overall survival outcomes but not with gender and age ( Bi and Wang, 2021 ).…”

“…In a previous study, RT-qPCR analysis revealed that LINC00472 levels in pancreatic cancer tissues were suppressed, relative to adjacent normal tissues ( Bi and Wang, 2021 ). Moreover, the study identified correlations between LINC00472 low expressions and TNM stages, lymph node metastases and overall survival outcomes but not with gender and age ( Bi and Wang, 2021 ). A stable LINC00472 overexpressing PANC-1 cell line was established and subcutaneously inoculated into nude mice models to validate the in vivo effects of LINC00472.…”

“…This gene sequence can be transcribed into four different transcripts: NR_121,614.1, NR_121,613.1, NR_026,807.2 and NR_121,612.1 ( Figure 1 ). LINC00472 is a novel LncRNAs that is closely associated with tumorigenesis and tumor progression in various cancers including breast cancer (BC) ( Shen et al, 2015a ; Lu et al, 2018 ; Wang et al, 2019a ; Li et al, 2021a ; Shao et al, 2021 ), lung cancer (LC) ( Su et al, 2018 ; Mao et al, 2019 ; Zou et al, 2019 ; Deng et al, 2020 ), hepatocellular carcinoma (HCC) ( Chen et al, 2019 ), osteosarcoma (OS) ( Zhang et al, 2020 ), colorectal cancer (CRC) ( Ye et al, 2018 ), epithelial ovarian cancer (OC) ( Fu et al, 2016 ), pancreatic cancer (PC) ( Bi and Wang, 2021 ), and gastric cancer (GC) ( Tsai et al, 2019 ). As a tumor suppressor, LINC00472 suppresses cell proliferation, migration as well as invasion.…”

“…Up-regulated LINC00472 levels in nude mice injected with oe-LINC00472–treated cells were confirmed. Tumor growth curves, tumor images as well as weights showed that overexpressed LINC00472 inhibits in vivo tumorigenesis ( Bi and Wang, 2021 ). Moreover, overexpressed LINC00472 suppresses Ki-67 levels.…”