MiR‑495 suppresses cell proliferation by directly targeting HMGA2 in lung cancer

Sun, Jing; Qiao, Yanping; Song, Tao; Wang, Haiwen

doi:10.3892/mmr.2018.9773

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…Upregulated expression of miR-495 significantly downregulated the mRNA and protein expression levels of HMGA2 in A549 cells, and then suppressed the proliferation of lung cancer cells. 53 These above studies all indicated that miRNA is an important regulatory mechanism for the expression of HMGA2. It is reasonable to speculate that the rs8756 A>C in the 3ʹ UTR of the HMGA2 gene may affect some miRNA's binding to HMGA2, thereby alternating gene expression level.…”

Section: Discussionmentioning

confidence: 91%

HMGA2 Gene rs8756 A>C Polymorphism Reduces Neuroblastoma Risk in Chinese Children: A Four-Center Case-Control Study

Liu

Hua

Cheng

et al. 2020

OTT

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Background: Neuroblastoma, mainly affecting children, is a lethal malignancy arising from the developing sympathetic nervous system. The genetic etiology of neuroblastoma remains mostly obscure. High mobility group AT-hook 2 (HMGA2), an oncogenic gene, is up-regulated in many tumors. Single nucleotide polymorphisms (SNPs) often modify cancer susceptibility. However, no studies are investigating the association between HMGA2 SNPs and neuroblastoma susceptibility. Methods: We conducted a four-center case-control study to evaluate the association between three HMGA2 polymorphisms (rs6581658 A>G, rs8756 A>C and rs968697 T>C) and neuroblastoma susceptibility in a Chinese population with 505 cases and 1070 controls. Logistic regression was performed to evaluate the strength of the association. Results: We found that the rs8756 AC/CC genotypes were associated with a reduced neuroblastoma risk when compared to rs8756 AA genotype [Adjusted odds ratio (OR) =0.74, 95% confidence interval (CI)=0.56-0.99, P=0.039]. Carriers with 3 protective genotypes have lower neuroblastoma susceptibility than those without or with 0-2 protective genotypes. The stratified analysis revealed that the protective effects of rs8756 AC/CC genotypes were more predominant among children of age > 18 months, males, and subgroups with the tumor in the mediastinum. Furthermore, haplotype analysis uncovered that haplotype ACC significantly reduced neuroblastoma risk. Conclusion: Our study indicated HMGA2 rs8756 A>C polymorphism is significantly associated with decreased neuroblastoma risk.

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Section: Discussionmentioning

confidence: 91%

HMGA2 Gene rs8756 A>C Polymorphism Reduces Neuroblastoma Risk in Chinese Children: A Four-Center Case-Control Study

Liu

Hua

Cheng

et al. 2020

OTT

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“…HMGA2 is reported to be an oncogene that has been extensively studied in diverse tumors, such as colon, breast, and gastric cancer (Li et al, ;Mansoori et al, ;Sun, Qiao, Song, & Wang, ;Xi et al, ). HMGA2 can bind to the promoter of the cyclin gene, upregulates cyclin expression, accelerates the G2/M phase of the cell cycle, and enhances tumorigenesis (Fusco & Fedele, ).…”

Section: Discussionmentioning

confidence: 99%

Circ_0000267 promotes gastric cancer progression via sponging MiR‐503‐5p and regulating HMGA2 expression

Cai

Nie

Chen

et al. 2019

Molec Gen & Gen Med

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Background: Circular RNAs (circRNAs) are a class of newly discovered RNAs that attach great importance to modulate gene expression and biological function.Nonetheless, in gastric cancer (GC), the expression and function of circRNA are much less explored. In this study, circ_0000267 expression in GC was investigated and the function and mechanism of circ_0000267 was probed. Materials and Methods: Quantitative real-time PCR (qRT-PCR) was employed to detect circ_0000267, miR-503-5p, and HMGA2 expression. Immunohistochemistry and western blot were adopted to detect HMGA2 and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and N-cadherin) expression in GC tissues and cells, respectively. GC cell lines with circ_0000267 overexpressed and knocked down were constructed, and CCK-8 assay, BrdU assay, scratch healing assay, and transwell assay were employed to assess the effect of circ_0000267 on the proliferation and metastasis of GC cells. Besides, dual-luciferase reporter gene assay was adopted to verify the targeting relationship between circ_0000267 and miR-503-5p. Results: Circ_0000267 showed a significant upregulation in GC tissues and cell lines, and its high expression level was extremely linked to the increased tumor diameter and local lymph node metastasis. Circ_0000267 overexpression accelerated GC cell proliferation, metastasis, and EMT processes, while knocking down circ_0000267 led to the opposite effect. From the perspective of mechanism, circ_0000267 promoted the progression of GC through adsorbing miR-503-5p and upregulating HMGA2 expression. Conclusion: Circ_0000267 is an oncogenic circRNA that affects the progression of GC, which participates in promotion of GC proliferation, migration, invasion, and EMT via modulating the miR-503-5p/HMGA2 axis. K E Y W O R D Scirc_0000267, Gastric cancer, HMGA2, miR-503-5p 2 of 12 | XIAOPENG Et Al. F I G U R E 2 circ_0000267 promoted GC cell proliferation, movement, migration, and invasion. (a) circ_0000267 plasmid was transfected into MGC-803 cells, and circ_0000267 in SGC-7901 cells was knocked down with siRNA, and the transfection efficiency was examined by qRT-PCR. (b-d) The proliferation of GC cells was examined using the CCK-8 assay and the BrdU assay. (e, f) Scratch healing experiments were used to detect the movement of GC cells. (g) Transwell assay was used to detect GC cell migration and invasion. (h) Western blot was used to detect the expression of EMT-related marker molecules, including E-cadherin and N-cadherin.

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“…Because of the relative stability of miRNA expression, some studies have used miRNAs as biomarkers [28]. Recent studies have found that miR-495 was involved in the tumorigenesis and progression of various cancers, including lung cancer [11], nasopharyngeal carcinoma [29], osteosarcoma [30], and melanoma [31]. All of these studies have identified miR-495 as a tumor suppressor.…”

Section: Il-11 Rescues the Inhibition Of Cell Proliferation Mediated mentioning

confidence: 99%

“…The main treatments for NSCLC are surgery, radiotherapy, and chemotherapy, but the efficacy is limited for advanced stages [10]. In addition, the molecular mechanisms underlying NSCLC development have yet to be fully elucidated [11]. The exploration of molecular mechanism may help develop targeted therapy, a new treatment option for advanced NSCLC, which can not only improve treatment efficacy but also reduce some adverse effects [12].…”

Section: Introductionmentioning

confidence: 99%

“…miR-495 is abnormally expressed in multiple types of human cancers. For example, it is up-regulated in bladder cancer [16] and down-regulated in gastric cancer [3], lung cancer [11], hepatocellular carcinoma [17], and breast cancer [18]. Although miR-495 was reported to be downregulated in NSCLC, the expression level and roles of miR-5688, which is located in the same cluster as miR-495, have yet to be completely elucidated in NSCLC.…”

Section: Introductionmentioning

confidence: 99%

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miR‐495 and miR‐5688 are down‐regulated in non‐small cell lung cancer under hypoxia to maintain interleukin‐11 expression

Zhao

Chang

Liu

et al. 2020

Cancer Communications

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Background Hypoxia is a hallmark of cancer and is associated with poor prognosis. However, the molecular mechanism by which hypoxia promotes tumor progression remains unclear. MicroRNAs dysregulation has been shown to play a critical role in the tumor and tumor microenvironment. Here, we investigated the roles of miR‐495 and miR‐5688 in human non‐small cell lung cancer (NSCLC) and their underlying mechanism. Methods The expression levels of miR‐495 and miR‐5688 in human NSCLC tissue specimens were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). Deferoxamine (DFO) was used to determine whether the regulation of miR‐495 and miR‐5688 under hypoxia was dependent on hypoxia‐inducible factor 1‐alpha (HIF‐1α). Furthermore, the functions of miR‐495 and miR‐5688 in tumor progression were evaluated using colony formation, 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS), wound healing, transwell assays, and xenograft model. Two algorithms, PicTAR and Targetscan, were used to predict the target gene of these two miRNAs, and dual‐luciferase reporter assay was conducted to confirm the target. The unpaired two‐tailed t test, Pearson correlation analysis, and Fisher's exact probability test were performed for statistical analyses. Results Two miRNAs, miR‐495 and miR‐5688, were found to participate in NSCLC progression under hypoxia. They were down‐regulated in NSCLC tissues compared with normal tissues. We determined that hypoxia led to the down‐regulation of miR‐495 and miR‐5688 in NSCLC cells, which was independent of HIF‐1α and cellular metabolic energy. In addition, miR‐495 and miR‐5688 suppressed cell proliferation, migration, and invasion in vitro. The NSCLC xenograft model showed that miR‐495 and miR‐5688 inhibited tumor formation in vivo. Interestingly, we found that miR‐495 and miR‐5688 had the same target, interleukin‐11 (IL‐11). Recombinant human IL‐11 counteracted the effects of miR‐495 and miR‐5688 on NSCLC cells, suggesting that miR‐495 and miR‐5688 executed their tumor suppressive role by repressing IL‐11 expression. Conclusion We found that hypoxia down‐regulated the expression levels of miR‐495 and miR‐5688 in NSCLC to enhance IL‐11 expression and tumor progression, indicating that the miR‐495/miR‐5688/IL‐11 axis may serve as a therapeutic target and potential biomarker for NSCLC.

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MiR‑495 suppresses cell proliferation by directly targeting HMGA2 in lung cancer

Cited by 14 publications

References 41 publications

<p><em>HMGA2</em> Gene rs8756 A>C Polymorphism Reduces Neuroblastoma Risk in Chinese Children: A Four-Center Case-Control Study</p>

<p><em>HMGA2</em> Gene rs8756 A>C Polymorphism Reduces Neuroblastoma Risk in Chinese Children: A Four-Center Case-Control Study</p>

Circ_0000267 promotes gastric cancer progression via sponging MiR‐503‐5p and regulating HMGA2 expression

miR‐495 and miR‐5688 are down‐regulated in non‐small cell lung cancer under hypoxia to maintain interleukin‐11 expression

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