miR-93-5p/IFNAR1 axis promotes gastric cancer metastasis through activating the STAT3 signaling pathway

Accumulating evidence has indicated that lncRNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1 which are responsible for human gastric cancer (GC) is still largely unknown. Here, we observed that NEAT1 and STAT3 expression were significantly upregulated in human gastric cancer cells including BGC823, SGC-7901, AGS, MGC803 and MKN28 cells compared to normal gastric epithelial cells GES-1 while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration and invasion of gastric cancer cells. Reversely, overexpression of NEAT1 exhibited an increase ability of gastric cancer progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate expression of NEAT1 in vitro. STAT3 was predicted as an mRNA target of miR-506 and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain gastric cancer development by decreasing STAT3 which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a ceRNA to modulate STAT3 by sponging miR-506 in gastric cancer. In conclusion, we implied that NEAT1 can serve as an important biomarker in gastric cancer diagnosis and treatment. This article is protected by copyright. All rights reserved.

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA NEAT1‐modulated miR‐506 regulates gastric cancer development through targeting STAT3

Tan

Wang

Liu

et al. 2019

“…One of the major regulatory mechanisms of miRNAs is the inhibition of gene expression through binding to the 3′UTR of target mRNAs. 8,9,14 A number of studies have reported that miRNAs exerted antitumor functions in cancers in such manner, 10,35 including in ESCC. 4,36 MiR-488-3p has also been reported to inhibit tumor progression by targeting oncogene in glioma and melanoma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐488‐3p inhibits proliferation and induces apoptosis by targeting ZBTB2 in esophageal squamous cell carcinoma

Yang

et al. 2019

Esophageal squamous cell carcinoma (ESCC) is the eighth most prevalent cancer and the sixth leading cause for cancer‐associated mortality. MicroRNAs (miRNAs) are increasingly reported to exert important regulatory functions in human cancers by regulating certain gene expression. miR‐488‐3p has been identified to be a tumor suppressor in multiple cancers, but its role in ESCC is yet to be investigated. The present study aimed to uncover the biological role and modulatory mechanism of miR‐488‐3p in ESCC. We first revealed the downregulation of miR‐488‐3p in ESCC tissues and cell lines. Gain‐of‐function assays confirmed that miR‐488‐3p overexpression abrogated proliferation and accelerated apoptosis. Mechanistically, we identified via bioinformatics tool and confirmed that zinc finger and BTB domain containing 2 (ZBTB2) was a target for miR‐488‐3p. Moreover, miR‐488‐3p activated the p53 pathway through suppressing ZBTB2. Finally, rescue assays proved that ZBTB2 was involved in the regulation of miR‐488‐3p on proliferation and apoptosis in ESCC. Additionally, we verified that miR‐488‐3p had alternate targets in ESCC by confirming the involvement of protein kinase, DNA‐activated, catalytic subunit (PRKDC), a known target for miR‐488‐3p, in miR‐488‐3p‐mediated regulation on ESCC. In sum, this study revealed that miR‐488‐3p inhibited proliferation and induced apoptosis by targeting ZBTB2 and activating p53 pathway in esophageal squamous cell carcinoma, providing a novel biological target for ESCC.

“…Separately, 11 studies from eight articles 15,[56][57][58][59][60][61][62] were included in the diagnostic meta-analysis and 14 studies from 13 articles 15,24,29,41,47,51,[63][64][65][66][67][68][69] were included in the prognostic meta-analysis. After screening the titles and abstracts, 476 articles were excluded because they were reviews (n = 18), meta-analyses (n = 5), nonhuman studies (n = 14), or studies irrelevant to our topic (n = 439).…”

Section: The Basic Characteristic Of Meta-analysismentioning

confidence: 99%

Molecular mechanism and role of microRNA‐93 in human cancers: A study based on bioinformatics analysis, meta‐analysis, and quantitative polymerase chain reaction validation

Gao

Deng

Liu

et al. 2018

Introduction Currently, studies have shown that microRNA‐93 (miR‐93) can be an oncogene or a tumor suppressor in different kinds of cancers. The role of miR‐93 in human cancers is inconsistent and the underlying mechanism on the aberrant expression of miR‐93 is complicated. Methods We first conducted gene enrichment analysis to give insight into the prospective mechanism of miR‐93. Second, we performed a meta‐analysis to evaluate the clinical value of miR‐93. Finally, a validation test based on quantitative polymerase chain reaction (qPCR) was performed to further investigate the role of miR‐93 in pan‐cancer. Results Gene Ontology (GO) enrichment analysis results showed that the target genes of miR‐93 were closely related to transcription, and MAPK1, RBBP7 and Smad7 became the hub genes. In the diagnostic meta‐analysis, the overall sensitivity, specificity, and area under the curve were 0.76 (0.64‐0.85), 0.82 (0.64‐0.92), and 0.85 (0.82‐0.88), respectively, which suggested that miR‐93 had excellent performance on the diagnosis for human cancers. In the prognostic meta‐analysis, dysregulated miR‐93 was found to be associated with poor OS in cancer patients. In the qPCR validation test, the serum levels of miR‐93 were upregulated in breast cancer, breast hyperplasia, lung cancer, chronic obstructive pulmonary disease, nasopharyngeal cancer, hepatocellular cancer, gastric ulcer, endometrial cancer, esophageal cancer, laryngeal cancer, and prostate cancer compared with healthy controls. Conclusions miR‐93 could act as an effective diagnostic and prognostic factor for cancer patients. Its clinical value for cancer early diagnosis and survival prediction is promising.