Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells

Shi, Yi; Zhao, Yang; Shao, Nan; Ye, Runyi; Lin, Yin; Zhang, Ning; Li, Wen; Zhang, Yunjian; Wang, Shenming

doi:10.3892/ol.2017.6025

Cited by 48 publications

(48 citation statements)

References 76 publications

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“…Six miRNAs were identified in the present study, and the results showed that the levels of miR-96-5p, miR-222-5p, and miR-652-5p were overexpressed, while miR-125-5p, miR-145-3p, and miR-379-3p levels were down-regulated in GAC sample. Several studies have demonstrated that miR-96-5p is overexpressed in various cancers, including colorectal cancer [13], pancreatic carcinoma [14], prostate cancer [15], hepatocellular carcinoma [16], and breast cancer [17], and it is oncogene that promotes cell proliferation. It has been reported that miR-652-5p is associated with non-small cell lung cancer [18], esophageal adenocarcinoma [19], and breast cancer [20], while the mechanism of miR-652-5p was not elaborated.…”

Section: Discussionmentioning

confidence: 99%

miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

Wang¹,

Liu

Meng

2020

Bioscience Reports

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Objective: To explore the biological function and mechanism of miR-96-5p in gastric cancer. Methods: The expression of differently expressed microRNAs (DEMs) related to gastric adenocarcinoma (GAC) prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR. A target gene miR-96-5p was selected using TargetScan, miRTarBase, miRDB databases. The combination of miR-96-5p and ZDHHC5 was verified by luciferase receptor assay. To further study the function and mechanism of miR-96-5p, we treated MGC-803 cells with miR-96-5p inhibitor and si-ZDHHC5, then detected cell viability, apoptosis, migration and invasion ability, as well as the expression of ZDHHC5, Bcl-2, Bax, cleaved caspase-3, cleaved caspase-9, and COX-2 by Western blot. Results: Compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p were significantly reduced in GAC tumor samples (P<0.01), which were consistent with bioinformatics analysis. Furthermore, ZDHHC5 was defined as a direct target gene of miR-96-5p. miR-96-5p silence significantly reduced cell viability, increased cell apoptosis, and suppressed cell migration and invasion, as well as inhibited the expression of Bcl-2 and COX-2 and promoted Bax, cleaved caspase-3 and cleaved caspase-9 level in MGC-803 cells (P<0.01). Notably, ZDHHC5 silence reversed the inhibiting effects of miR-96-5p on MGC-803 cells growth and metastasis Conclusion: Our findings identified six microRNAs (miRNAs; miR-96-5p, miR-222-5p, miR-652-5p, miR-125-5p, miR-145-3p, and miR-379-3p) related to GAC prognosis, and suggested that down-regulated miR-96-5p might inhibit tumor cell growth and metastasis via increasing ZDHHC5 expression enhance MGC-803 cell apoptosis, as well as decrease MGC-803 cell metastasis.

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Section: Discussionmentioning

confidence: 99%

miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

Wang¹,

Liu

Meng

2020

Bioscience Reports

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“…As a consequence of that, miRNA-96 silencing induces an increase in γ-globin [32,33]. In addition, overexpression of miRNA-96-5p inhibits autophagy and apoptosis in human breast cancer cells [34]. Thus, although our results are referred to RBCs, this evidence could indicate that miRNA-96 decrease might be a sign of ongoing RBC autophagy and apoptosis.…”

Section: Discussionmentioning

confidence: 44%

MicroRNA Dysregulation Associated with Red Blood Cell Storage

Chen

Xie

Xing

et al. 2018

Transfus Med Hemother

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Introduction: Stored red blood cells (RBCs) undergo storage lesions involving morphological, physiological and biochemical changes. MicroRNAs (miRNAs) have important functions in cell apoptosis and life processes. Therefore, the aim of this study was to explore potential roles of miRNAs in the damage of stored RBCs. Methods: Blood samples were collected from 13 healthy male O-type donors, and leuko-reduced RBCs were divided into fresh RBC group and 20-day storage RBC group. Results: Eight predicted miRNAs with modified expressions with an intersection ≥ 3 were found dysregulated in the 20-day storage RBC group and involved in apoptosis and senescence signaling pathway: miR-31-5p, miR-196a-5p, miR-203a, miR-654-3p and miR-769-3p were increased, while miR-96-5P, miR-150-5P and miR-197-3p were decreased. Evidence associating miR-31-5p, miR-203a, miR-654 and miR-769 to RBCs or blood in general are not available. Conclusions: Dysregulated miRNAs might represent potential biomarkers to identify storage lesions, and their detection might help to evaluate the quality of stored RBCs.

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“…In consistent with these studies, the present study shows that miR-192-5p could target FOXO1, and its dysregulation was involved in hyperglycemia and insulin resistance. Indeed, it has been shown that the expression of FOXO1 and acetylated-FOXO1 is regulated by miR-96-5p in human breast cancer cell [13]. These studies suggest that the expression of FOXO1 is regulated by different miRNAs.…”

Section: Discussionmentioning

confidence: 92%

“…It has been documented that FOXO1 is regulated by miRNA. For example, it has been reported that miR-96-5p inhibited autophagy via downregulation of the expression of FOXO1 and acetylated-FOXO1 in human breast cancer cell [13]. However, the relationship between circHIPK3 and FOXO1/diabetes remains largely unknown.…”

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confidence: 99%

Circular RNA HIPK3 contributes to hyperglycemia and insulin homeostasis by sponging miR-192-5p and upregulating transcription factor forkhead box O1

et al. 2020

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It has been shown that circular RNAs, a class of non-coding RNA molecules, play an important role in the regulation of glucose and lipid homeostasis. In the present study, we sought to investigate the function of circular RNA HIPK3 (circHIPK3) in diabetes-associated metabolic disorders, including hyperglycemia and insulin resistance. Results show that oleate stimulated circHIPK3 increase, and that circHIPK3 enhanced the stimulatory effect of oleate on adipose deposition, triglyceride (TG) content, and cellular glucose content in HepG2 cells. MiR-192-5p was the potential target of circHIPK3, since circHIPK3 significantly decreased miR-192-5p mRNA level, whereas anti-circHIPK3 significantly increased miR-192-5p mRNA level. Further study shows that transcription factor forkhead box O1 (FOXO1) was a downstream regulator of miR-192-5p, since miR-192-5p significantly decreased FOXO1 expression, whereas circHIPK3 significantly increased FOXO1 expression. Notably, the inhibitory effect of miR-192-5p was significantly reversed by circHIPK3. In vivo study shows that anti-miR-192-5p significantly increased blood glucose content, which was significantly inhibited by FOXO1 shRNA. MiR-192-5p significantly decreased adipose deposition and TG content in HepG2 cells, which was significantly reversed by the co-treatment with circHIPK3. Forskolin/dexamethasone (FSK/DEX) significantly increased cellular glucose, mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), and this stimulatory effect of FSK/DEX was significantly inhibited by miR-192-5p. In the presence of circHIPK3, however, the inhibitory effect of miR-192-5p was totally lost. In summary, the present study demonstrated that circHIPK3 contributes to hyperglycemia and insulin resistance by sponging miR-192-5p and up-regulating FOXO1.

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Overexpression of microRNA-96-5p inhibits autophagy and apoptosis and enhances the proliferation, migration and invasiveness of human breast cancer cells

Cited by 48 publications

References 76 publications

miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

miR-96-5p enhances cell proliferation and invasion via targeted regulation of ZDHHC5 in gastric cancer

MicroRNA Dysregulation Associated with Red Blood Cell Storage

Circular RNA HIPK3 contributes to hyperglycemia and insulin homeostasis by sponging miR-192-5p and upregulating transcription factor forkhead box O1

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