MicroRNA-421 inhibits caspase-10 expression and promotes breast cancer progression

Tb, Hu; Hs, Chen; Mq, Cao; Fd, Guo; Xy, Cheng; Zb, Han; Mq, Li

doi:10.4149/neo_2018_170306n159

Cited by 28 publications

(21 citation statements)

References 16 publications

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“…Recent studies have revealed the aberrant expression of various miRNAs in breast cancer, and their deregulation has been implicated in breast cancer genesis and development (11)(12)(13). Deregulated miRNAs can have oncogenic or tumor-suppressive roles in breast cancer and control biological behaviors, including cell proliferation, cell cycle, apoptosis, invasion, metastasis, epithelial-mesenchymal transition and angiogenesis (14)(15)(16). Therefore, further investigations of the biological functions of miRNAs may help us to better understand the mechanisms underlying breast cancer formation/progression and facilitate the development of attractive therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

et al. 2018

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Numerous studies have revealed that a subset of microRNAs (miRNAs) is aberrantly expressed in breast cancer. The dysregulation of miRNAs is involved in the tumorigenesis and progression of breast cancer due to their negative regulation of downstream target genes. Therefore, the identification of deregulated miRNAs in breast cancer may provide important insights into the diagnosis and treatment of patients with this disease. miRNA-511 (miR-511) has been identified to be deregulated in diverse human cancer types; however, neither the expression status nor the detailed roles of miR-511 in breast cancer have been clarified. Thus, it was aimed to determine the expression of miR-511 in breast cancer, examine the role in malignant progression and explore its downstream targets. The results of the present study revealed that the expression of miR-511 was downregulated in breast cancer tissues and cell lines. Decreased expression of miR-511 was significantly associated with lymph node metastasis and tumor stage in patients with breast cancer. Functional analyses revealed that restoring miR-511 expression suppressed breast cancer cell proliferation and colony formation, promoted apoptosis and reduced metastasis in vitro, while it attenuated tumor growth in vivo. Additionally, it was revealed that SRY-box 9 (SOX9) was a direct target gene of miR-511 in breast cancer cells. SOX9 was upregulated in breast cancer tissues and its expression was inversely correlated with that of miR-511. Furthermore, SOX9 inhibition simulated the tumor-suppressive roles of miR-511 overexpression in breast cancer cells, while SOX9 reintroduction partially rescued these effects of miR-511. Notably, the upregulation of miR-511 targeted SOX9 to deactivate the PI3K/Akt signaling in breast cancer in vitro and in vivo. In conclusion, miR-511 was downregulated in breast cancer, and impeded its malignant progression by directly targeting SOX9 and regulating the PI3K/Akt pathway. Thus, miR-511 is a potential therapeutic target in breast cancer.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

et al. 2018

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“…Increased miR-421 expression has also been reported in other malignancies, such as breast cancer and gastric cancer. 31 , 32 Moreover, the increased expression of miR-421 was first demonstrated to be associated with positive lymph-node metastasis and advanced TNM stage in NSCLC patients. These results indicate that miR-421 is a candidate oncogene and may be involved in tumor development in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Upregulated expression of miR-421 is associated with poor prognosis in non-small-cell lung cancer

Cui

et al. 2018

CMAR

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BackgroundNon-small-cell lung cancer (NSCLC) represents the most frequent subtype of lung cancer. MicroRNAs (miRNAs) have attracted a lot of attention with regard to their clinical significance and crucial biological functions in various human cancers. This study aimed to investigate the prognostic significance of microRNA-421 (miR-421) and its correlation with tumor progression in NSCLC.Materials and methodsExpression levels of miR-421 in both serum and tissue samples were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The prognostic value of miR-421 was evaluated using Kaplan–Meier survival analysis and Cox regression assay. To explore the functional role of miR-421 during NSCLC progression, cell experiments were carried out.ResultsExpression of serum and tissue miR-421 was upregulated in the NSCLC patients compared with the normal controls (all P<0.001), and the expression showed a significant correlation between the serum samples and tissues (R=0.475, P<0.001). The increased miR-421 expression was associated with positive lymph-node metastasis and advanced TNM stage (all P<0.05). Moreover, patients with high miR-421 expression had poor overall survival compared with those with low expression (log-rank P=0.007). The overexpression of miR-421 proved to be an independent prognostic factor for NSCLC (HR=1.991, 95% CI=1.046–3.791, P=0.036). According to the cell experiments, the proliferation, migration and invasion of NSCLC cells were suppressed by knockdown of miR-421.ConclusionOverexpression of miR-421 serves as a prognostic biomarker and may be involved in the promotion of tumor progression in NSCLC.

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“…There were several limitations existed in our study. Firstly, the differential expression of miR-421 has been previously reported in other cancer, including breast cancer, cervical cancer, and hepatocellular carcinoma [34][35][36]. The results demonstrated that miR-421 might not be particularly relevant to GC itself, it is also associated with the progression of other common cancers.…”

Section: Gastric Cancer (Gc) Is Listed As One Of the Most Common Malimentioning

confidence: 81%

Identifying the diagnostic value of microRNA-421 in gastric cancer patients: a meta-analysis

Yan

Zhang

Wang

et al. 2018

Preprint

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Objectives.Emerging evidence has shown that the expression level of microRNA-421 (miR-421) was significantly different between gastric cancer (GC) patients and healthy individuals. However, the diagnostic accuracy of miR-421 in the reports remains inconsistent. This meta-analysis aims to assess the diagnostic value of miR-421 in GC detection. Methods.All related articles on miR-421 in GC diagnosis were retrieved until September 2018. The QUADAS-2 checklist was used to assess the methodological quality of each study. The diagnostic performance of miR-421 for GC were assessed by using Meta-DiSc 1.4 and STATA 14.0 statistical software. Results.A total of 172 GC patients and 154 healthy controls from three articles (four studies) were enrolled in this meta-analysis. The results of pooled sensitivity, specificity, diagnostic odds ratio (DOR) with 95% confidence interval (CI) were 0.90 (95% CI: 0.85 to 0.93), 0.83 (95% CI: 0.77 to 0.87), and 37.18 (95% CI: 8.61 to 160.49), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.8977. Conclusions.This study indicates that miR-421 could serve as a promising biomarker for GC detecting. Further studies are needed to verify the generalizability of these findings.

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MicroRNA-421 inhibits caspase-10 expression and promotes breast cancer progression

Cited by 28 publications

References 16 publications

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

MicroRNA-511 inhibits malignant behaviors of breast cancer by directly targeting SOX9 and regulating the PI3K/Akt pathway

Upregulated expression of miR-421 is associated with poor prognosis in non-small-cell lung cancer

Identifying the diagnostic value of microRNA-421 in gastric cancer patients: a meta-analysis

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