Functional analyses of microRNA-326 in breast cancer development

Du, Ye; Shen, Lishengnan; Zhang, Wei; Ding, Rongbo; Li, Qian; Li, Simin; Zhang, Haipeng

doi:10.1042/bsr20190787

Cited by 16 publications

(14 citation statements)

References 27 publications

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“…Likewise, previous evidence has shown that miR-326 may act as an anti-tumor miR in the occurrence and development of human prostatic carcinoma (10). Consistent with our findings, miR-326 was down-regulated in the tissues and cell lines of human BC, and the overexpressed miR-326 has been showed to inhibit the cell proliferation, migration, and invasion of BC (11). Besides, miR-326 has been reported to be poorly expressed in gastric cancer cells and overexpression of miR-326 inhibits the proliferation of gastric cancer cells (29).…”

Section: Discussionsupporting

confidence: 92%

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A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition

Zhao

et al. 2020

Front. Oncol.

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Background: Breast cancer (BC) represents a heterogeneous disease with distinct subtypes and high tumor metastatic potentials. Recent researchers identify the implication of circular RNAs (circRNAs) in the initiation of BC. Herein, we uncover a novel circRNA hsa_circRPPH1_015 as a tumor promoter in BC. Methods: A total of 86 paired cancerous and non-cancerous tissues were surgically resected and collected from BC patients. Cell proliferation, colony formation, and cell invasion were examined by Edu staining, clone formation assays, propidium iodide (PI)-labeled flow cytometry, and Transwell invasion assays. PCNA, Ki67, MMP-2, MMP-9, Cyclin D1, and CDK4 expression was assayed using Western blot analysis. RNA pull-down, dual-luciferase reporter gene assay, and RNA binding protein immunoprecipitation (RIP) assay were performed to investigate the relationships among hsa_circRPPH1_015, microRNA-326 (miR-326), and ELK1. The tumor growth of human BC MCF-7 cells in vivo was evaluated in nude mice by subcutaneous xenografts of MCF-7 cells. Results: hsa_circRPPH1_015 expression was upregulated in BC tissues. Knockdown of hsa_circRPPH1_015 restrained the aggressive behavior of MCF-7. hsa_circRPPH1_015 could bind to miRNA-326 that negatively regulates ELK1. Elevation of miRNA-326 expression resulted in inhibition of cell proliferation, colony formation, and cell invasion of MCF-7. Disturbance of miRNA-326 or overexpression of ELK1 restored the proliferation and aggressiveness in hsa_circRPPH1_015-depleted MCF-7 cells. Tumor growth of MCF-7 cells in vivo was reduced in nude mice lack of endogenous hsa_circRPPH1_015 expression. Conclusion: Overall, the present study demonstrates that hsa_circRPPH1_015 was an oncogene and unfavorable prognostic factor in BC, providing an exquisite therapeutic target for BC.

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Section: Discussionsupporting

confidence: 92%

“…miR-326 highlights itself as an antioncomiR in pro-static carcinoma by negatively regulates Mucin1 (10). Additionally, miR-326 has been noted to harbor tumor-suppressive property in BC (11). Furthermore, the TargetScan database revealed that there were binding sites between miR-326 and ETS-domain containing protein (ELK1).…”

Section: Introductionmentioning

confidence: 99%

A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition

Zhao

et al. 2020

Front. Oncol.

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“…Recent studies have found that the levels of miR-326 are lower in breast cancer tissues (32,33). In particular, a recent study by our team found that miR-326 functions as a tumor suppressor in breast cancer by targeting SOX12 (34). The RT-qPCR results showed that overexpression of miR-326 significantly decreased SNHG3 expression whereas depletion of SNHG3 obviously increased miR-326 levels in the assayed cells.…”

Section: Discussionmentioning

confidence: 81%

lncRNA SNHG3 promotes breast cancer�progression by acting as a miR‑326 sponge

et al. 2020

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Accumulating evidence suggests that long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SHNG3) plays crucial roles in the initiation and progression of various types of malignant cancers. Yet, the role played by SNHG3 in breast cancer as well as the associated mechanisms remain largely unclear. The expression of SNHG3 was detected in breast cancer tissues and cell lines by reverse-transcription quantitative PCR (RT-qPCR). Cell proliferation, colony formation, cell cycle distribution, migration and invasion abilities were detected by Cell Counting Kit-8, colony formation assay, flow cytometry, wound-healing and Matrigel invasion assays, respectively. The regulatory relationships between SNHG3 and miR-326 were explored by luciferase reporter assay. A nude mouse model was established to investigate the effect of SNHG3 in vivo. The results showed an upregulation of SNHG3 in breast cancer tissues and cell lines. Loss-of-function assays revealed significant suppression of breast cancer behaviors such as: Abilities to proliferate, form colonies, migrate and invade in vitro coupled with a delayed growth of tumors in vivo when SNHG3 was knocked down. Mechanically, it was shown that SNHG3 served as a competing endogenous RNA (ceRNA) of miR-326 that in turn is a tumor suppressor in this cancer. The correlation between the expression of SNHG3 and miR-326 was found to be strongly negative in these samples. Additionally, we found that inhibition of SNHG3 caused a partially reversal in the inhibition exerted by miR-326 on the ability of these cells to proliferate, form colonies, migrate and invade. Collectively, these findings suggest the functioning of SNHG3 as a ceRNA to enhance the ability of breast cancer cells to proliferate and metastasize to putatively serve as a new target to explore therapeutic intervention of this malignancy.

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“…For instance, miR-326 targets ErbB/PI3K and SOX12 to repress BC cell proliferation, migration and invasion. 14,15 It should be noted that circRNAs participate in affecting tumor progression by interacting with miRNAs. 35 There are also accumulating studies demonstrating that circRNA adsorbs miRNAs, thus taking part in the development in BC.…”

Section: Discussionmentioning

confidence: 99%

“…13 In addition, some studies indicate that miR-326 is downregulated in BC. 14,15 This implies that miR-326 functions as the tumor suppressor in BC. It is worth noting that bioinformatics predicts the potential binding site between circ_0000291 and miR-326, suggesting that circ_0000291 may regulate the expression of miR-326, but this mechanism is still unclear.…”

Section: Introductionmentioning

confidence: 99%

The circRNA circ_0000291 acts as a sponge of microRNA 326 to regulate E26 transformation‐specific sequence‐1 expression and promote breast cancer progression

Min

Pan

Liu

2020

Pathology International

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Accumulating studies authenticate that circular RNAs (circRNAs) are involved in the progression of cancers. However, their role in breast cancer (BC) remains largely unknown. In this study, real‐time polymerase chain reaction was employed to detect the circ_0000291 and miR‐326 expressions in BC tissues and cells. The correlation between the expression level of circ_0000291 and clinicopathological parameters of BC patients was analyzed. Western blot was used to detect the expression of E26 transformation‐specific sequence‐1 (ETS1), E‐cadherin, N‐cadherin and Vimentin in BC cells. Cell proliferation was measured using the cell counting kit‐8 assay and the bromodeoxyuridine assay. Cell migration and invasion were detected by Transwell assay. The interactions between circ_0000291 and miR‐326, miR‐326 and ETS1 were verified using bioinformatics prediction, the dual‐luciferase reporter gene assay or/and RNA binding protein immunoprecipitation assay. We demonstrated that circ_0000291 was significantly upregulated in BC, and its high expression was positively correlated with T stage and local lymph node metastasis. Functional assays validated that circ_0000291 promoted BC cell proliferation, migration and invasion. The mechanism studies indicated that circ_0000291 could decoy miR‐326 and in turn upregulate the expression of ETS1. In conclusion, circ_0000291 is the novel oncogenic circRNA and promotes BC progression via modulating the miR‐326/ETS1 axis.

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Functional analyses of microRNA-326 in breast cancer development

Cited by 16 publications

References 27 publications

A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition

A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition

lncRNA SNHG3 promotes breast cancer�progression by acting as a miR‑326 sponge

The circRNA circ_0000291 acts as a sponge of microRNA 326 to regulate E26 transformation‐specific sequence‐1 expression and promote breast cancer progression

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