Inhibition of invasion and migration of prostate cancer cells by miRNA-509-5p via targeting MDM2

Tian, Xin; Luo, Yizhao; He, Peng; Li, J.; Ma, Zhiwei; An, Yu

doi:10.4238/gmr16019195

Cited by 11 publications

(6 citation statements)

References 25 publications

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“…The important function of MDM2-p53 axis in the development of cancer led to the discovery of potential anti-cancer approaches that disrupted the interaction of p53 with MDM2 or targeted MDM2. Notably, MDM2 was also identified as the targets of miRNAs that modulated the growth of cancer cells 25,26. For example, recent study showed that miR-758-3p suppressed the proliferation, migration and invasion of hepatocellular carcinoma cells by targeting MDM2 27.…”

Section: Introductionmentioning

confidence: 99%

<p>miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2</p>

Cai¹,

Hao²,

Ren³

et al. 2019

CMAR

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BackgroundIncreasing evidence has suggested the critical implication of microRNAs (miRNAs) in the initiation and progression of non-small cell lung cancer (NSCLC). Previous studies have shown the tumor-suppressive function of miR-1305 in cancer; however, the role of miR-1305 in NSCLC has not been fully understood.MethodsThe expression of miR-1305 in NSCLC was detected by RT-qPCR. The influence of miR-1305 on the growth of NSCLC cells was determined via Cell Counting Kit 8 (CCK-8), colony formation and FACS analysis. The targets of miR-1305 were predicted with the miRDB database. Luciferase reporter assay was performed to investigate the binding between miR-1305 and 3ʹ-UTR of MDM2. Western blot was applied to check the expression of MDM2 with miR-1305.ResultsHere, we found that miR-1305 was down-regulated in NSCLC tissues and cell lines. Decreased miR-1305 was significantly correlated with the metastasis and poor prognostics of NSCLC patients. Overexpression of miR-1305 inhibited the proliferation and migration and promoted the apoptosis of NSCLC cells. Bioinformatics and luciferase assay uncovered that the mouse/murine double minute 2 (MDM2) was a target of miR-1305. miR-1305 bound the 3ʹ-untranslated region (UTR) of MDM2 and decreased the expression of MDM2 in NSCLC cells. As MDM2 was a negative regulator of p53, decreased MDM2 by miR-1305 up-regulated the abundance of p53 in NSCLC cells. Restoration of MDM2 markedly attenuated the suppressive role of miR-1305 in the proliferation and migration of NSCLC cells.ConclusionThe findings provided novel mechanism of miR-1305/MDM2 signaling in regulating the progression of NSCLC, suggesting miR-1305 as a promising target for the treatment of NSCLC.

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Section: Introductionmentioning

confidence: 99%

<p>miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2</p>

Cai¹,

Hao²,

Ren³

et al. 2019

CMAR

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“…Previous studies have shown that the downregulated expression of miRNA may be essential in the onset and development of PCa ( 21 – 23 ). In addition, increased expressed of miRNA was likely to regulate the expression of target genes and exert its influences on the progression of PCa ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of miR‑224‑5p in prostate cancer and its relevant molecular mechanism via TCGA, GEO database and in�silico analyses

Gan

Zhang

et al. 2018

Oncol Rep

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The function of the expression of microRNA (miR)-224-5p in prostate adenocarcinoma (PCa) remains to be elucidated, therefore, the present study aimed to investigate the clinical significance and potential molecular mechanism of miR-224-5p in PCa. Data on the expression of miR-224-5p in PCa were extracted from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), ArrayExpress and previous literature, and meta-analyses with standardized mean difference (SMD) and summary receiver operating characteristic (sROC) methods were performed for statistical analyses. The prospective target genes of miR-224-5p were collected by overlapping the differentially expressed mRNAs in TCGA and GEO, and target genes predicted by miRWalk2.0. Subsequently, in silico analysis was performed to examine the associated pathways of miR-224-5p in PCa. The expression of miR-224-5p was markedly lower in PCa; the overall SMD was −0.562, and overall sROC area under the curve was 0.80. In addition, Kyoto Encyclopedia of Genes and Genomes analysis revealed that the prospective target genes of miR-224-5p were largely enriched in the amino sugar and nucleotide sugar metabolism signaling pathway, and three genes [UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), hexokinase 2 (HK2) and chitinase 1 (CHIT1)] enriched in this pathway showed higher expression (P<0.05). In addition, key genes in the protein-protein interaction network analysis [DNA topoisomerase 2-α (TOP2A), ATP citrate lyase (ACLY) and ribonucleotide reductase regulatory subunit M2 (RRM2)] exhibited significantly increased expression (P<0.05). The results suggested that the downregulated expression of miR-224-5p may be associated with the clinical progression and prognosis of PCa. Furthermore, miR-224-5p likely exerts its effects by targeting genes, including UAP1, HK2, CHIT1, TOP2A, ACLY and RRM2. However, in vivo and in vitro experiments are required to confirm these findings.

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“…For instance, upregulation MDM2 has been detected in non-small cell lung cancer, gastric cancer and bladder cancer, acting as a sponge of miR-1305, miR-410 and miR-379-5p, respectively ( 36 – 38 ). Additionally, the 3′-UTR of MDM interacts with miRNA-509-5p and miR-129 to modulate the progression of prostate cancer and glioma ( 39 , 40 ). The data from the present study confirmed that MDM2 was upregulated in PC tissues and the 3′-UTR of MDM2 is a direct target of miR-2113.…”

Section: Discussionmentioning

confidence: 99%

lncRNA MNX1‑AS1 promotes prostate cancer progression through regulating miR‑2113/MDM2 axis

Dong¹,

Tian

Zhang

2022

Mol Med Rep

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A growing number of dysregulated long non-coding (lnc)RNAs have been verified to serve an essential role in human prostate cancer. However, the underlying mechanisms of lncRNA MNX1 Antisense RNA 1 (MNX1-AS1) in prostate cancer has not been explored. Therefore, the present study aimed to explore the function of MNX1-AS1 in prostate cancer tumorigenesis and investigate the in-depth mechanism. The expression of MNX1-AS1, microRNA (miR)-2113 and murine double min 2 (MDM2) in prostate cancer tissues and corresponding normal tissues were assessed by reverse transcription-quantitative PCR. The protein expression levels of MDM2 were detected by western blotting. LNCaP and PC-3 cells were transfected with short hairpin (sh)-MNX1-AS1, miR-2113 mimics, miR-2113 inhibitor and pCDH-MDM2 vector using Lipofectamine ® 3000. Cell proliferation, migration and invasion abilities were assessed by CCK-8 assay, colony formation and Transwell assay, respectively. Dual luciferase reporter assay was carried out to confirm the putative targets of MNX1-AS1 and miR-2113. Tumor formation experiment in nude mice was applied to evaluate the tumor growth effect of MNX1-AS1 in vivo . The expression of MNX1-AS1 was significantly upregulated in the prostate cancer tissues and cell lines. MNX1-AS1 knockdown suppressed the abilities of cell viability and migration and invasion in vitro and inhibited tumor growth in vivo . Additionally, luciferase reporter assay revealed that MNX1-AS1 could target miR-2113 and negatively interacted with miR-2113 in prostate cancer cells. miR-2113 directly targeted to MDM2 and negatively modulated the expression of MDM2. Rescue assays suggested that the viability, migration and invasion of impaired cells triggered by transfection with sh-MNX1-AS1 alone could be recovered by co-transfection with sh-MNX1-AS1 + miR-2113 inhibitor or sh-MNX1-AS1 + pCDH- MDM2 vector. The present study demonstrated that MNX1-AS1 promoted prostate cancer progression through regulating miR-2113/ MDM2 axis.

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Inhibition of invasion and migration of prostate cancer cells by miRNA-509-5p via targeting MDM2

Cited by 11 publications

References 25 publications

<p>miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2</p>

<p>miR-1305 Inhibits The Progression Of Non-Small Cell Lung Cancer By Regulating MDM2</p>

Downregulation of miR‑224‑5p in prostate cancer and its relevant molecular mechanism via TCGA, GEO database and in�silico analyses

lncRNA MNX1‑AS1 promotes prostate cancer progression through regulating miR‑2113/MDM2 axis

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