MicroRNA-544a Regulates Migration and Invasion in Colorectal Cancer Cells via Regulation of Homeobox A10

Sun, Shangfeng; Su, Changying; Zhu, Yunxiao; Li, Haiyan; Liu, Ning; Xu, Tong; Sun, Chao; Lv, Yanfeng

doi:10.1007/s10620-016-4186-2

Cited by 21 publications

(31 citation statements)

References 26 publications

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“…In a previous study, upregulated miR-544a was detected in metastatic tumor samples and cell lines of colorectal cancer. 22 Homeobox A10 is vital for the regulatory role of miR-544a in migration and invasion. 22 The boosting function of miR-544a on migration and invasion of gastric cancer cells can be mediated by the degradation and the translocation of β-catenin by modulating the expression of cadherin 1 and Axis inhibition protein 2.…”

Section: Discussionmentioning

confidence: 99%

“…22 Homeobox A10 is vital for the regulatory role of miR-544a in migration and invasion. 22 The boosting function of miR-544a on migration and invasion of gastric cancer cells can be mediated by the degradation and the translocation of β-catenin by modulating the expression of cadherin 1 and Axis inhibition protein 2. 23 An investigation by Lu et al found that miR-544a could counteract cadherin 1 activity, leading to migration and invasion of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

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<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

Liu¹,

Yang²,

Cao³

et al. 2020

OTT

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Circular RNA (circRNA) is involved in the development of various cancers. However, whether circRNA can inhibit the tumorigenesis of non-small cell lung cancer (NSCLC) is still unclear. We aimed to explore the epigenetic function of tumor-suppressive circRNA (hsa_circ_RNA_0011780) and its downstream regulatory factors in NSCLC. Patients and Methods: Quantitative polymerase chain reaction (qPCR) was used to evaluate hsa_circ_11780 expression in NSCLC tissues and cell lines. The impact of high hsa_circ_11780 expression on overall survival in patients with NSCLC was tested using the Log rank test. The association between decreased hsa_circ_11780 expression and clinicopathological features in patients with NSCLC was analyzed using the Chi-squared test. In vitro cell proliferation and apoptosis were assayed using the cell counting kit-8 (CCK-8) and flow cytometry, respectively. Mice xenograft models were used to determine the tumor promoting effects of hsa_circ_11780 on NSCLC in vivo. The underlying regulatory mechanism was predicted by bioinformatics and verified by a dual-luciferase reporter assay, RNA transfection, qPCR, and Western blotting. The correlation between miR-544a and hsa_-circ_11780 expression was verified using Spearman correlation coefficient. Results: The expression of hsa_circ_11780 in NSCLC tissues and cell lines strongly declined. Low hsa_circ_11780 expression is more likely to present in patients with a large tumor size (>3cm), distant metastasis, and poor overall survival. hsa_circ_11780 overexpression strongly inhibited proliferation, migration, and invasion of NSCLC cells (H226 and A549) in vitro and inhibited tumor growth in vivo. Furthermore, hsa_circ_11780 repressed miR-544a function by competitively binding to the complementary sites of miR-544a. miR-544a released by the declining expression of hsa_circ_11780 reduced the protein concentration of F-Box and WD repeat domain containing 7 (FBXW7) in NSCLC cells. Conclusion: FBXW7 expression mediated by the hsa_circ_11780/miR-544a axis is markedly associated with the proliferation, migration, and invasion of NSCLC, resulting in decreased survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

Liu¹,

Yang²,

Cao³

et al. 2020

OTT

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“…HOXA family genes are well known as the crucial transcription factors in pathogenesis and development of AML. HOXA10 belongs to the HOXA gene superfamily, dysregulation of which has been observed in several solid tumors (38)(39)(40). HOXA10 plays a role in myeloid differentiation, leukemogenesis and chemoresistance in AML (41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia

Guo

Zhang

et al. 2020

Preprint

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Background HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. Methods We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. Results HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). Conclusions Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

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“…Therefore, we hypothesized that the transcriptional activity of the HOXA10 gene may be regulated in part by HOXA10-AS-directed DNA hypomethylation. Several miRNAs were also known to regulate HOXA10 expression in colorectal cancer ( 45 ), oral cancer ( 46 ), hepatocellular carcinoma ( 47 ) and breast cancer ( 48 ), suggesting that HOXA10-AS may function as a competing endogenous RNA (ceRNA) to regulate HOXA10 gene expression.…”

Section: Discussionmentioning

confidence: 99%

HOXA10‑AS: A novel oncogenic long non‑coding RNA in glioma

Dong

Cui

et al. 2018

Oncol Rep

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Glioma is the most common primary malignant tumor of the central nervous system. Emerging evidence has demonstrated that long non-coding RNAs (lncRNAs) serve a major role of regulation in various types of human cancer, including glioma. However, the biological roles of thousands of lncRNAs remain unknown and require further identification. The present study investigated the functional role of lncRNA-HOXA10-AS in glioma. The present study examined the expression patterns of HOXA10-AS in glioma and normal brain tissues, as well as glioma cell lines and normal human astrocytes (HA) via reverse transcription-quantitative polymerase chain reaction. HOXA10-AS knockdown cells were generated using lentiviral short hairpin RNA against HOXA10-AS in A172 and U251 glioma cells. Cell growth was assessed by MTT assay, and a flow cytometer was used to investigate cell proliferation, cell cycle distribution and cell apoptosis. Western blot analysis was performed to analyze the expression levels of apoptosis-related proteins. HOXA10-AS was significantly upregulated in glioma tissues and cell lines, and increased HOXA10-AS expression levels were associated with higher grades of glioma. Knockdown of HOXA10-AS inhibited glioma cell proliferation and increased cell apoptosis rates compared with the control cells. HOXA10-AS markedly regulated the expression of the homeobox A10 (HOXA10) gene. Similarly, HOXA10 expression was increased with higher grades of glioma, and silencing of HOXA10 by small interfering RNA suppressed glioma cell proliferation and induced cell apoptosis. The results of the present study demonstrated that HOXA10-AS promoted cell growth and survival through activation of HOXA10 gene expression in glioma, which may potentially act as a novel biomarker and therapeutic target for clinical assay development.

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MicroRNA-544a Regulates Migration and Invasion in Colorectal Cancer Cells via Regulation of Homeobox A10

Abstract: Our study demonstrates that miR-544a regulates invasive and metastatic properties of CRC cells by modulating HOXA10 expression level both in vitro and in vivo. miR-544a may represent a new therapeutic target for the intervention of metastatic colorectal cancer.

Cited by 21 publications

References 26 publications

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

<p>Hsa_circ_RNA_0011780 Represses the Proliferation and Metastasis of Non-Small Cell Lung Cancer by Decreasing FBXW7 via Targeting miR-544a</p>

Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia

HOXA10‑AS: A novel oncogenic long non‑coding RNA in glioma

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