miR-26a/HOXC9 Dysregulation Promotes Metastasis and Stem Cell-Like Phenotype of Gastric Cancer

Peng, Xudong; Kang, Qingjie; Wan, Rui; Wang, Ziwei

doi:10.1159/000493502

Cited by 24 publications

(17 citation statements)

References 22 publications

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“…In the present study, lower miR-26a expression was significantly associated with diffuse type GC, but the relationship between miR-26a and Lauren's classification is controversial. While higher miR-26a expression was reported to be associated with diffuse type GCs 35 , others reported downregulated miR-26a in poorly differentiated GCs 36 . More research is needed to clarify how miRNA functions in tumorigenesis according to Lauren's classification.…”

Section: Discussionmentioning

confidence: 95%

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Kim

Jang

Heo

et al. 2020

Sci Rep

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Understanding cancer-prone environments is important to efficiently detect and prevent cancers. The associations between miRNA and cancer-prone environments are still largely unknown in gastric cancer (GC). Six miRNAs that are differentially expressed during gastric carcinogenesis were selected, and quantitative real-time pcR was performed in an independent training set (fresh non-tumor and tumor samples from 18 GC patients) and validation sets (set 1 with formalin-fixed paraffin-embedded non-tumor and tumor samples from 19 solitary GC and set 2 with 37 multiple GC patients). The results were compared with those of 37 gastric mucosa from 20 healthy volunteers. The expression levels of miR-26a, miR-375, and miR-1260 in gastric mucosa from healthy volunteers were statistically higher than that of non-tumorous gastric mucosa located 3 cm apart from the GC in the training set (miR-26a, P < 0.0001; miR-375, P = 0.0049; miR-1260, P = 0.0172), validation set 1 (miR-26a and miR-375, P < 0.0001; miR-1260, P = 0.0008), and validation set 2 (miR-26a, miR-375, and miR-1260, P < 0.0001). And a combination of miR-26a and miR-1260 showed the highest area under the curve value of 0.89. miRNAs are differentially expressed in non-neoplastic gastric mucosa and can be used as a biomarker to predict cancer-prone environments.

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Section: Discussionmentioning

confidence: 95%

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Kim

Jang

Heo

et al. 2020

Sci Rep

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“…The miR-182/HOXA9 axis is implicated in RUNX3-mediated GC development [51]. In addition, HOXC9 contributes to GC progression by inducing EMT, MMP2 expression, and stem cell-like properties [29]. HOXC10 activates ATM/NF-kB pathway and MAPK signalling, functioning as an oncogene in GC [30,54].…”

Section: Mechanisms By Which Hox Proteins Regulate Gcmentioning

confidence: 99%

Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

Jin

Dai

et al. 2020

BMC Cancer

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Background An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC. Methods A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored. Conclusions HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.

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“…MicroRNAs (miRNAs/miRs) can function as oncogenes or tumor suppressor genes, and regulate gene expression through translational repression or mRNA degradation by binding to the 3'-untranslated region (3'UTR) of their target mRNAs (5,6). Previous studies have identified that miRNAs exhibit aberrant expression and serve essential roles in GC (7)(8)(9)(10). Therefore, further investigation into the expression and function of miRNAs may improve understanding of the molecular mechanisms responsible for the pathogenesis of GC.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA‑520a‑3p inhibits the proliferation, migration and invasion via spindle and kinetochore associated 2 in gastric cancer

Ren

Jiang

et al. 2019

Oncol Lett

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MicroRNAs (miR) serve important roles in the development and progression of tumors by targeting different genes. miR-520a-3p reported in lung and breast cancers as a tumor suppressor gene. However, the expression and functional significance of miR-520a-3p is not completely understood in gastric cancer (GC). In the present study, it was demonstrated that the expression levels of miR-520a-3p were significantly downregulated in GC tissues and cells using RT-qPCR. In addition, downregulated expression of miR-520a-3p was associated with the clinical stage of the tumor and invasion in patients with GC. Furthermore, overexpression of miR-520a-3p significantly inhibited cell proliferation, invasion and migration in SGC-7901 and MGC-803 GC cell lines using proliferation, wound healing and cell invasion assays. Spindle and kinetochore associated 2 (SKA2) was upregulated in GC cells using western blot analysis and a target gene of miR-520a-3p; miR-520a-3p mimics significantly reduced SKA2 expression. In addition, upregulation of SKA2 protein expression SKA2 reversed the miR-520a-3p-mediated inhibition of SGC-7901 cell proliferation, migration and invasion. In conclusion, miR-520a-3p functioned as a tumor suppressor gene by targeting SKA2 in GC cell lines, and may serve as a novel prognostic and potential therapeutic marker.

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miR-26a/HOXC9 Dysregulation Promotes Metastasis and Stem Cell-Like Phenotype of Gastric Cancer

Cited by 24 publications

References 22 publications

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Dysregulated miRNA in a cancer-prone environment: A study of gastric non-neoplastic mucosa

Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

Upregulation of microRNA‑520a‑3p inhibits the proliferation, migration and invasion via spindle and kinetochore associated 2 in gastric cancer

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