miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells

Kim, Yu Jin; Jeong, Seongtae; Jung, Woon Yong; Choi, Jung Won; Hwang, Ki Chul; Kim, Sang Woo; Lee, Yong Chan

doi:10.7150/ijms.42654

Cited by 18 publications

(14 citation statements)

References 20 publications

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“…Additionally, another study examining a total of 2573 patients also suggested that overexpression of miR-92a serves as an unfavorable prognostic indicator in LUAD patients [35]. To our knowledge, miR-27b-5p had been reported as a tumor suppressor in ovarian carcinoma and oral cancer [20,36], but it is highly expressed in gastric adenocarcinoma and may play a positive role in tumorigenesis and development [37]. However, regrettably, no study has reported the relationship between Evidence-Based Complementary and Alternative Medicine miR-27b-5p and lung cancer.…”

Section: Discussionmentioning

confidence: 85%

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a

Chi

Meng

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Lung adenocarcinoma (LUAD) is one of the most prevalent malignancies. However, its mechanism and therapeutic strategy remain to be clarified. Mangiferin is a flavonoid derived from the leaves of mango trees of the lacquer family that has many pharmacological and physiological effects. This research aimed to elucidate the biological effect of mangiferin in LUAD cell lines and clarify the in vitro mechanism of mangiferin. Mangiferin was shown to significantly restrain the proliferation of LUAD cells (A549, H1299, and H2030 cells) in a dose- and time-dependent manner. Furthermore, mangiferin was capable of stimulating apoptosis, and more cells were blocked in G1 and S phase in the mangiferin-treated cells than in those not treated with mangiferin. Microarrays and micro-RNA sequencing data suggested that there is a higher level of miR-27b and miR-92a in LUAD tissues than in non-LUAD tissues. Additional experiments indicated that mangiferin may be related to the downregulated levels of miR-92a and miR-27b. In conclusion, mangiferin likely regulates proliferation and apoptosis in LUAD cells by reducing the expression levels of miR-92a and miR-27b.

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Section: Discussionmentioning

confidence: 85%

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a

Chi

Meng

Chen

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…In addition, bioinformatics analysis and luciferase reporter assay proved that miR-29b-1-5p was the downstream target of HOTAIRM1. Kim et al demonstrated that miR-29b-1-5p, acting as a GC development promoter, regulated GC cell migration by targeting CREBZF (Kim et al 2020). Additionally, it has been reported that the lower expression of miR-29b-1-5p reduced the IC50 of human breast cancer parental cell line MCF-7 selected at 500 nM Adriamycin, and the higher expression of miR-29b-1-5p weakened the effects of liposomal curcumin to Adriamycin-resistance (Zhou et al 2017).…”

Section: Discussionmentioning

confidence: 99%

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells Via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Chen

et al. 2021

Preprint

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Background Our previous study has shown that Da0324, a curcumin analog, has significantly improved stability and antitumor activity. However, the molecular mechanisms of action of Da0324 remains poorly understood. Long non-coding RNA (lncRNA) has been certifed to play a key role in tumor progression. Here, we aim to investigate the molecular mechanisms underlying the anti-cancer activities of Da0324 through regulation of lncRNA HOTAIRM1. Methods Gastric cancer cell lines were treated with Da0324 and/or transfected with lentiviral vector expressing HOTAIRM1 shRNA, and/or miR-29b-1-5p mimics and/or small interference RNA (siRNA) against PHLPP1, or HOTAIRM1 siRNA or lentiviral vector expressing HOTAIRM1, as required. The expression of HOTAIRM1, miR-29b-1-5p and PHLPP1 in GC cells were determined by Real-Time PCR. Cell growth was examined by CCK-8 assay and colony formation assay in vitro. The targeted relationship between HOTAIRM1 and miR-29b-1-5p was verifed by luciferase reporter gene assay. Western blot was utilized to investigate PHLPP1 protein expression levels. Results Da0324 increased the expression of HOTAIRM1 in GC cells. HOTAIRM1 expression was significantly down-regulated in GC tissues, and the low expression of HOTAIRM1 was associated with the shorter survival rate of GC patients based on TCGA database. Knockdown of HOTAIRM1 promoted GC cell proliferation whereas overexpression of HOTAIRM1 inhibited GC cell proliferation as detected by CCK-8 and colony formation assays. Moreover, knockdown of HOTAIRM1 reversed the Da0324-mediated growth inhibition of GC cells. Furthermore, HOTAIRM1 acted as a sponge for miR-29b-1-5p and PHLPP1 is regulated by the HOTAIRM1/miR-29b-1-5p axis in GC cells. Overexpression of miR-29b-1-5p or knockdown of PHLPP1 reversed the ability of Da0324 to inhibit the growth of GC cells. Conclusions Our data suggest that Da0324 exerts antitumor activity by regulating HOTAIRM1/miR-29b-1-5p/PHLPP1 axis in GC cell, and provide new insights into the anti-cancer mechanism of Da0324.

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“…Moreover, gene FBXO11 , XPO1 , SLC3A2 , and APC , whose mutation detections may be affected by various tumor purities in gastric cancer, were closely related with cancer occurrence and development. For examples, protein FBXO11 has both the E3 ubiquitin ligase and methyltrasferase activity, which could facilitate epithelial-mesenchymal transition (EMT), promote PI3K/AKT pathway activation, and regulate metastasis and apoptosis in human cancer ( Kim et al, 2018 , 2020 ; Sun et al, 2018 ). Protein XPO1 is positively correlated with cell proliferation and growth transformation, and negatively correlated with poor survival outcomes, which could be a promising molecular target in gastric cancer ( Subhash et al, 2018 ; Gruffaz et al, 2019 ; Sexton et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

Cheng

Wang

et al. 2020

Front. Mol. Biosci.

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The non-cancerous components in tumor tissues, e.g., infiltrating stromal cells and immune cells, dilute tumor purity and might confound genomic mutation profile analyses and the identification of pathological biomarkers. It is necessary to systematically evaluate the influence of tumor purity. Here, using public gastric cancer samples from The Cancer Genome Atlas (TCGA), we firstly showed that numbers of mutation, separately called by four algorithms, were significant positively correlated with tumor purities (all p < 0.05, Spearman rank correlation). Similar results were also observed in other nine cancers from TCGA. Notably, the result was further confirmed by six in-house samples from two gastric cancer patients and five in-house samples from two colorectal cancer patients with different tumor purities. Furthermore, the metastasis mechanism of gastric cancer may be incorrectly characterized as numbers of mutation and tumor purities of 248 lymph node metastatic (N + M0) samples were both significantly lower than those of 121 non-metastatic (N0M0) samples (p < 0.05, Wilcoxon rank-sum test). Similar phenomena were also observed that tumor purities could confound the analysis of histological subtypes of cancer and the identification of microsatellite instability status (MSI) in both gastric and colon cancer. Finally, we suggested that the higher tumor purity, such as above 70%, rather than 60%, could be better to meet the requirement of mutation calling. In conclusion, the influence of tumor purity on the genomic mutation profile and pathological analyses should be fully considered in the further study.

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miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells

Cited by 18 publications

References 20 publications

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a

Mangiferin Inhibits Human Lung Adenocarcinoma by Suppressing MiR-27b and MiR-92a

The Curcumin Analog Da0324 Inhibits the Proliferation of Gastric Cancer Cells Via HOTAIRM1/miR-29b-1-5p/PHLPP1 Axis

Biased Influences of Low Tumor Purity on Mutation Detection in Cancer

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