MicroRNA‑140‑5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β‑catenin signaling pathway

Cha, Yinlian; He, Ying; Ouyang, Kaobin; Xiong, Hua; Li, Jun; Yuan, Xia

doi:10.3892/ol.2018.9480

Cited by 22 publications

(19 citation statements)

References 19 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the popular action mechanisms of lncRNAs is to serve as a competing endogenous RNA (ceRNA) to regulate the expression and function of target genes by binding and sequestering with miRNAs. 13 Among many miRNAs, miR-140-5p was selected as a candidate for further analysis since several publications have reported its tumor-suppressive role in GC, [14][15][16] and in this study, we confirmed that TMPO-AS1 negatively regulated miR-140-5p expression in GC cells, and the oncogenic effects of TMPO-AS1 overexpression on GC cells were partially reversed by miR-140-5p restoration. MiRNAs exert their functions by negative regulation of their target genes, 17 and this study further showed that miR-140-5p directly targets SOX4, a master mediator of EMT in GC cells.…”

Section: Discussionsupporting

confidence: 81%

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer</p>

Sun¹,

Han²

2020

CMAR

View full text Add to dashboard Cite

Background: Mounting evidence show that long non-coding RNAs (lncRNAs) play critical roles in the progression of various human cancers, including gastric cancer (GC), a common gastrointestinal tumor. In this study, the biological functions of lncRNA TMPO-AS1 in GC were studied. Methods: TMPO-AS1 and miR-140-5p expression levels were detected in GC tissues and cell lines by RT-qPCR analysis. Knockdown or overexpression of TMPO-AS1 was conducted to evaluate the effects of TMPO-AS1 on the malignant behaviors of GC cells. Bioinformatic prediction and dual-luciferase reporter assay were performed to investigate the direct interaction between TMPO-AS1 and miR-140-5p in GC. Results: We observed that TMPO-AS1 was up-regulated in GC tissues, and high TMPO-AS1 expression in GC patients was closely correlated with aggressive clinicopathologic characteristics and poor overall survival. Functionally, gain-and loss-of-function studies showed that TMPO-AS1 overexpression enhanced the proliferation, migration, invasion and EMT of GC cells in vitro, whereas knockdown of TMPO-AS1 inhibited these malignant traits. Importantly, we demonstrated that TMPO-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-140-5p in GC cells, thereby diminishing the inhibition on SOX4, an EMT regulator. Conclusion: Our findings indicated that TMPO-AS1 promotes GC progression partly by regulating miR-140-5p/SOX4 axis, and may serve as a novel therapeutic target for GC.

show abstract

Section: Discussionsupporting

confidence: 81%

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer</p>

Sun¹,

Han²

2020

CMAR

View full text Add to dashboard Cite

show abstract

“…Having shown that Wnt1 is a marker of adaptive immune tolerance in human LUAD, we sought to investigate its relevance to other types of cancers. We focused on colon, breast, hepatocellular, gastric and renal clear cell carcinomas, due to their reported associations with Wnt1 [24][25][26][27][28] . The abundance of CD8 + T cells can be measured by expression of the signature genes CD8a and CD8b 29 .…”

Section: Resultsmentioning

confidence: 99%

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

et al. 2019

View full text Add to dashboard Cite

Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associates with T cell abundance. Altering Wnt1 expression profoundly affects growth of murine lung adenocarcinomas and this is dependent on conventional dendritic cells (cDCs) and T cells. Mechanistically, Wnt1 leads to transcriptional silencing of CC/CXC chemokines in cDCs, T cell exclusion and cross-tolerance. Wnt-target genes are up-regulated in human intratumoral cDCs and decrease upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-nanoparticles given as single therapy or part of combinatorial immunotherapies act at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 induces immunologically cold tumors through cDCs and highlight its immunotherapeutic targeting.

show abstract

“…In addition, miR-140-5p inhibits invasion and migration of FaDu cells by targeting A disintegrin and metalloproteinase 10 in the Notch1 signaling pathway (28). miR-140-5p also inhibits gastric cancer by regulating the WNT1-mediated WNT/β-catenin signaling pathway (30).…”

Section: Introductionmentioning

confidence: 99%

Downregulated microRNA‑140‑5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800

et al. 2020

View full text Add to dashboard Cite

Despite advances in the diagnosis and treatment in recent years, lung cancer is still one of the primary causes of cancer-associated morbidity and mortality in globally. Abnormally expressed microRNAs (miRNAs/miRs) in tumor tissues serve vital roles in the pathological mechanism of tumors and have become prospective biomarkers for cancer diagnosis. The present study aimed to investigate the effects of the miR-140-5p/zinc finger protein 800 (ZNF800) axis in lung carcinoma, and determine its potential underlying molecular mechanisms. The degree of cell proliferation was assessed via the MTT assay, while the migratory and invasive abilities of lung cancer cells were determined via the Transwell and Matrigel assays. The expression levels of miR-140-5p and ZNF800 were detected via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that miR-140-5p expression was notably higher in normal human bronchial epithelial cells compared with the respective lung cancer cell lines, H292, PC-9, CL1-5 and H460. Furthermore, miR-140-5p expression increased in the lung cancer cells compared with the control cells following transfection with miR-140-5p mimic. Overexpressing miR-140-5p significantly suppressed the proliferative, invasive and migratory abilities of H460 and PC-9 cells, and stimulated cell apoptosis by upregulating the expression of cleaved-caspase-3. Notably, these effects were reversed following transfection with miR-140-5p inhibitor. miR-140-5p was predicted as a negative regulator of ZNF800, and ZNF800 knockdown significantly suppressed the proliferative and metastatic abilities of lung adenocarcinoma (LUAD) cells, which was comparable to the effects of miR-140-5p mimic. Taken together, these results suggest that miR-140-5p may block the malignant phenotype of LUAD by negatively regulating ZNF800 expression. Thus, the miR-140-5p/ZNF800 axis may be used as an alternative therapeutic target for lung carcinoma in general, and LUAD in particular.

show abstract

MicroRNA‑140‑5p suppresses cell proliferation and invasion in gastric cancer by targeting WNT1 in the WNT/β‑catenin signaling pathway

Cited by 22 publications

References 19 publications

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer</p>

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer</p>

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma

Downregulated microRNA‑140‑5p expression regulates apoptosis, migration and invasion of lung cancer cells by targeting zinc finger protein 800

Contact Info

Product

Resources

About