miR-33a-5p inhibits the progression of esophageal cancer through the DKK1-mediated Wnt/β-catenin pathway

Song, Qingping; Liu, Hui; Li, Chengyan; Liang, Haifeng

doi:10.18632/aging.203430

Cited by 14 publications

(10 citation statements)

References 33 publications

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“…However, as the dose response of miR-33a-5p deletion in GC is not clear, it is difficult to determine its corresponding biological response in GC. Many studies have found that miR-33a-5p plays a regulatory role in variety of tumors [12,16]. To explore the miR-33a-5p effect in GC cells, we confirmed the expression, potential targets by QRT-PCR, western blot, and luciferase assay.…”

Section: Discussionmentioning

confidence: 76%

“…Many studies have found that miR-33a-5p plays a regulatory role in variety of tumors [ 12 , 16 ]. To explore the miR-33a-5p effect in GC cells, we confirmed the expression, potential targets by QRT-PCR, western blot, and luciferase assay.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, differential expression of miRNA is involved in the development of some tumors [ 11 ]. For example, miR-33a-5p blocks the progression of esophageal cancer by KK1-Wnt/ β -catenin axis [ 12 ]. PD-L1 inhibitor can regulate the miR-33a-5p/PTEN axis and increase the sensitivity of glioblastoma to radiation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

et al. 2022

Disease Markers

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Objective. The objective of this study is to explore the effects of microRNA-33a-5p (miR-33a-5p)-ras-related protein Rap-2a (RAP2A) on biological functions of gastric cancer (GC) and to find the potential functional mechanism. Methods. We measured the miR-33a-5p expression in 30 GC tissues and cellular level and 30 adjacent normal tissues as control. Besides, the expression of miR-33a-5p was checked at cell level as well. To screen the possible targets of miR-33a-5p, prediction software was used and gene RAP2A attracted our attention. Through a series of experiments including real-time polymerase chain reaction (qRT-PCR), luciferase assay, and western blotting (WB), we verified RAP2A as a potential target of miR-33a-5p. The impacts of miR-33a-5p and RAP2A on biological functions of GC cell lines (BGC-823 and MGC-803) were analyzed by subsequent experiments. Cell invasion was tested by invasion assays. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Cell clone was measured by clone formation assays. Finally, the expression of RAP2A protein was analyzed by WB assay. Results. We found miR-33a-5p was expressed lowly in GC tissues and cells. Overexpression of miR-33a-5p in BGC-823 and MGC-803 cells greatly inhibited the cell invasion and colony number. Furthermore, compared to sh-control (shControl), RAP2A knockdown (sh-RAP2A/shRAP2A) raised the sensitivity of GC cells to 5-FU significantly, characterized as reducing cell apoptosis. Conclusions. The expression of miR-33a-5p was lower in GC cell lines and tissues obviously, indicating that miR-33a-5p served as the antitumor gene in GC. The expression of RAP2A regulated negatively the sensitivity of GC cells to 5-FU. According to our in vitro experiments, miR-33a-5p/RAP2A was likely to become a new therapeutic target for GC.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

et al. 2022

Disease Markers

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“…Likewise, DKK1 was identified as a direct target of miR-372 and miR-373 in breast cancer and CRC cells, and knockdown of DKK1 promoted the growth and invasive activity of cancer cells ( Zhou et al, 2012 ). Many other miRNAs, in addition to the ones mentioned above, have been identified as related to DKK1, including miR-9, miR-31, miR-33a-5p, miR-34a, miR-92b, miR-101, miR-103a-3p, miR-130b-3p, miR-152, miR-291a-3p, miR-302b, miR-373-3p, miR-410, miR-433-3p, miR-488, miR-493, miR-501-5p, miR-522, miR-523-3p, miR-543, miR-590-3p, miR-613, miR-3064-3p, and miR-BART10-3p ( Liu et al, 2016b ; Fan et al, 2016 ; Jia et al, 2016 ; Zhang et al, 2016 ; Feng et al, 2017 ; Lv et al, 2017 ; Tang et al, 2017 ; Weng et al, 2017 ; Wang et al, 2018a ; Wang et al, 2018b ; Chen et al, 2018 ; Zhao et al, 2018 ; Liu et al, 2019 ; Min and Lee, 2019 ; Wang et al, 2019 ; Li et al, 2020a ; Li et al, 2020b ; Liu et al, 2020 ; Xiang et al, 2020 ; Zeng et al, 2020 ; Zhou et al, 2020 ; Liao et al, 2021 ; Song et al, 2021 ; Wu et al, 2021 ).…”

Section: Dkk1 Inhibitorsmentioning

confidence: 99%

Drug Discovery of DKK1 Inhibitors

Jiang

Yu²,

Chu

et al. 2022

Front. Pharmacol.

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Dickkopf-1 (DKK1) is a well-characterized Wnt inhibitor and component of the Wnt/β-catenin signaling pathway, whose dysregulation is associated with multiple abnormal pathologies including osteoporosis, Alzheimer’s disease, diabetes, and various cancers. The Wnt signaling pathway has fundamental roles in cell fate determination, cell proliferation, and survival; thus, its mis-regulation can lead to disease. Although DKK1 is involved in other signaling pathways, including the β-catenin-independent Wnt pathway and the DKK1/CKAP4 pathway, the inhibition of DKK1 to propagate Wnt/β-catenin signals has been validated as an effective way to treat related diseases. In fact, strategies for developing DKK1 inhibitors have produced encouraging clinical results in different pathological models, and many publications provide detailed information about these inhibitors, which include small molecules, antibodies, and nucleic acids, and may function at the protein or mRNA level. However, no systematic review has yet provided an overview of the various aspects of their development and prospects. Therefore, we review the DKK1 inhibitors currently available or under study and provide an outlook on future studies involving DKK1 and drug discovery.

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“…Relevant studies have shown that miR-128-3p and miR-33a-5p, as tumor suppressor genes, can affect the occurrence, invasion, and metastasis of gastric cancer, esophageal cancer, breast cancer, colorectal cancer, melanomas, and other cancers, through different signaling pathways ( 20 - 23 ). In lung cancer, miR-33a-5p has been reported to inhibit the proliferation and invasion of lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

A test of miR-128-3p and miR-33a-5p in serum exosome as biomarkers for auxiliary diagnosis of non-small cell lung cancer

Li¹,

Liu²,

Cheng³

et al. 2023

J Thorac Dis

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Background Lung cancer is the malignant tumor with the highest incidence and mortality rate in the world today, and non-small cell lung cancer (NSCLC) is its most common type. However, there is still a paucity of specific tumor markers for lung cancer screening. Herein, we detected and compared the levels of miR-128-3p and miR-33a-5p in serum exosomes of NSCLC patients and healthy volunteers, with the aim of identifying suitable exosomal microRNAs (miRNAs) as tumor biomarkers, and explored their value in the auxiliary diagnosis of NSCLC. Methods All participants were recruited from September 1, 2022 to December 30, 2022, and met the inclusion criteria. The case group included 20 patients with lung nodules who were highly suspected of having lung cancer (two cases were excluded). A total of 18 healthy volunteers (control group) were also enrolled. Blood samples were collected in both the case group before surgery and in the control group. Quantitative real-time polymerase chain reaction method was used to detect the expression of miR-128-3p and miR-33a-5p in serum exosomes. The main indicators of statistical analysis included the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Results Compared with the healthy control group, the NSCLC case group had significantly lower expression levels of serum exosome miR-128-3p and miR-33a-5p (P<0.01, P<0.001), and there was a significant positive correlation between the two exosome miRNAs (r=0.848, P<0.01). The AUC values of miR-128-3p alone and miR-33a-5p alone in distinguishing case group and control group were 0.789 [95% confidence interval (CI): 0.637–0.940; sensitivity: 61.1%; specificity: 94.4%; P=0.003] and 0.821 (95% CI: 0.668–0.974; sensitivity: 77.8%; specificity: 83.3%; and P=0.001), respectively. The combination of miR-128-3p and miR-33a-5p had an AUC of 0.855 (95% CI: 0.719–0.991; P<0.001) for distinguishing case group and control group, which was greater than the AUC values of miR-128-3p alone and miR-33a-5p alone (cut-off value: 0.034; sensitivity: 83.3%; and specificity: 88.9%). However, there was no significant difference in the AUC among these three groups (P>0.05). Conclusions Serum exosome miR-128-3p and miR-33a-5p showed good performance in NSCLC screening and may be used as new biomarkers for large-scale NSCLC screening.

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miR-33a-5p inhibits the progression of esophageal cancer through the DKK1-mediated Wnt/β-catenin pathway

Cited by 14 publications

References 33 publications

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU

Drug Discovery of DKK1 Inhibitors

A test of miR-128-3p and miR-33a-5p in serum exosome as biomarkers for auxiliary diagnosis of non-small cell lung cancer

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