Long noncoding RNA HNF1A‐AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR‐363‐3p/MAP2K4

Abstract

Long noncoding RNAs (lncRNAs) have been proven to exert important functions in the various biological processes of human cancers. It has been reported that lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) was abnormally expressed and played a role in the initiation and development of various human cancers. In this study, we confirmed that the expression level of HNF1A-AS1 was increased in glioma tissues and cells. Knockdown of HNF1A-AS1 inhibited cell proliferation and promoted cell apoptosis in glioma. Then, we disclosed the downregulation of miR-363-3p in glioma tissues and cell lines. The interaction between HNF1A-AS1 and miR-363-3p was identified in glioma cells. Furthermore, an inverse correlation between HNF1A-AS1 and miR-363-3p was observed in glioma tissues. Afterwards, we recognized that MAP2K4 was a direct target of miR-363-3p. The expression of MAP2K4 was negatively correlated with miR-363-3p while positively related to HNF1A-AS1 in glioma tissues. We also found the regulatory effect of HNF1A-AS1 on the MAP2K4-dependent JNK signaling pathway. All findings indicated that HNF1A-AS1 induces the upregulation of MAP2K4 to activate the JNK signaling pathway to promote glioma cell growth by acting as a miR-363-3p sponge.

A Signature of Nine lncRNA Methylated Genes Predicts Survival in Patients With Glioma

“…Aberrant expression of lncRNAs has been observed in human cancers, where they can act as either tumor suppressor genes or oncogenes, depending on the environment in which tumor cells are located (9,10). Multiple studies have shown that the dysregulation of lncRNAs is extensively involved in the malignant progression of human cancers (11,12). In addition, lncRNAs also play a crucial role in the occurrence and development of glioma.…”

miR‐363‐3p induces EMT via the Wnt/β‐catenin pathway in glioma cells by targeting CELF2

“… 18 , 19 , 20 At present, only two studies examined the role of miR ‐ 363 ‐ 3p with glioma cells. Bi et al 21 reported that HNF1A‐AS1 promotes glioma cell growth by acting as a miR ‐ 363 ‐ 3p sponge. Xu et al 22 reported that miR ‐ 363 ‐ 3p promotes cell proliferation, protects against apoptosis, and enhances invasion by directly targeting PDHB in glioma cells.…”

MiR‐363‐3p promotes prostate cancer tumor progression by targeting Dickkopf 3

“…34 It has been documented that miR-363-3p is expressed aberrantly in various cancers, for instance glioma, liver cancer, along with non-small-cell lung cancer. [35][36][37] Furthermore, a recent investigation exhibited that miR-363-3p suppressed tumor progression by directly targeting SOX4 in osteosarcoma. 38 Nonetheless, The data illustrated that silencing of miR-363-3p dampened cell migration, infiltration and growth and suppressed apoptosis in PCa cell lines, while miR-363-3p overexpression led to the opposite influences.…”

“…Diverse investigations have illustrated that miRNAs participate in numerous biological processes, for instance cell growth, apoptosis, as well as differentiation 34 . It has been documented that miR‐363‐3p is expressed aberrantly in various cancers, for instance glioma, liver cancer, along with non‐small‐cell lung cancer 35–37 . Furthermore, a recent investigation exhibited that miR‐363‐3p suppressed tumor progression by directly targeting SOX4 in osteosarcoma 38 …”