Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163

Su, Lin; Han, Dongrui; Wu, Jingwen; Huo, Xueyun

doi:10.1007/s13277-015-4151-2

Cited by 62 publications

(58 citation statements)

References 32 publications

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“…Since miR-3163, miR-324-5p and miR-532-3p were the top three upregulated miRs shown by qPCR validation assay and the relationship of miR-3163/miR-324-5p to cancer were reported [8, 19, 20], we chose to study the role of miR-532-3p in the anti-cancer role of 20(S)-Rg3. We reported that 20(S)-Rg3 inhibited the Warburg effect in the ovarian cancer cells [10].…”

Section: Resultsmentioning

confidence: 99%

“…All the 11 upregulated miRs were consistently increased in qPCR assay as in deep sequencing profile. Among the top three upregulated miRs in qPCR results, miR-3163 and miR-324-5p were reported to exert negative roles in cancers [20, 35], miR-532-3p was largely undetermined in cancer and was therefore selected to be functionally examined here. As expected, 20(S)-Rg3 upregulated miR-532-3p and promoted its direct inhibition on HK2 expression and the Warburg effect.…”

Section: Discussionmentioning

confidence: 99%

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Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

Zhou

Zheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. Methods: microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells. miR-532-3p was overexpressed by mimic532-3p transfection in SKOV3 and A2780 cells or inhibited by inhibitor532-3p transfection in 20(S)-Rg3-treated cells to examine the changes in HK2 and PKM2 expression, glucose consumption, lactate production and cell growth. Dual-luciferase reporter assay was conducted to verify the direct binding of miR-532-3p to HK2. The methylation status in the promoter region of pre-miR-532-3p gene was examined by methylation-specific PCR. Expression changes of key molecules controlling DNA methylation including DNMT1, DNMT3A, DNMT3B, and TET1-3 were examined in 20(S)-Rg3-treated cells. DNMT3A was overexpressed in 20(S)-Rg3-treated cells to examine its influence on miR-532-3p level, HK2 and PKM2 expression, glucose consumption and lactate production. Results: Deep sequencing results showed that 11 microRNAs were increased and 9 microRNAs were decreased by 20(S)-Rg3 in SKOV3 cells, which were verified by qPCR. More than 2-fold increase of miR-532-3p was found in 20(S)-Rg3-treated SKOV3 cells. Forced expression of miR-532-3p reduced HK2 and PKM2 expression, glucose consumption and lactate production in SKOV3 and A2780 ovarian cancer cells. Inhibition of miR-532-3p antagonized the suppressive effect of 20(S)-Rg3 on HK2 and PKM2 expression, glucose consumption and lactate production in ovarian cancer cells. Dual-luciferase reporter assay showed that miR-532-3p directly suppressed HK2 rather than PKM2. miR-532-3p level was controlled by the methylation in the promoter region of its host gene. 20(S)-Rg3 inhibited DNMT3A expression while exerted insignificant effect on DNMT1, DNMT3B and TET1-3. 20(S)-Rg3 reversed DNMT3A-mediated methylation in the promoter of the host gene of miR-532-3p, and thus elevated miR-532-3p level followed by suppression of HK2 and PKM2 expression, glucose consumption and lactate production. Conclusions: 20(S)-Rg3 modulated microRNAs to exert the anti-tumor effect in ovarian cancer. 20(S)-Rg3 lessened the DNMT3A-mediated methylation and promoted the suppression of miR-532-3p on HK2 to antagonize the Warburg effect of ovarian cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

Zhou

Zheng

et al. 2018

Cell Physiol Biochem

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“…Transfection of a CCNA1 siRNA into NSCLC cell lines significantly increases the cell cycle arrest and apoptosis of NSCLC cells [60]. SKP2 overexpression in NSCLC tissues and the coordinate suppression of SKP2 by miR-3163 and Megs inhibit the growth of NSCLC tumors [61]. Decreased LDHA expression induced by ectopic miR-499a expression induces apoptosis and DNA damage when cells are exposed to ionizing radiation [62].…”

Section: Discussionmentioning

confidence: 99%

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments

et al. 2018

Cell Physiol Biochem

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Background/Aims: The purpose of this study was to probe the clinico-pathological significance and the underlying mechanism of miR-30d-5p expression in non-small cell lung cancer (NSCLC). Methods: We initially examined the level of miR-30d-5p expression in NSCLC and non-cancer tissues using RT-qPCR. Then, a series of validation analyses including a meta-analysis of data from microarray chips in Gene Expression Omnibus (GEO), data mining of the cancer genome atlas (TCGA) and an integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies were performed to examine the clinico-pathological value of miR-30d-5p expression in NSCLC. In vitro experiments were further conducted to investigate the impact of miR-30d-5p on NSCLC cell growth. The molecular mechanism by which miR-30d-5p regulates the pathogenesis of NSCLC was probed through a bioinformatics analysis of its target genes. Moreover, dual luciferase reporter assay was conducted to verify the targeting regulatory relationship between miR-30d-5p and CCNE2. Results: Based on results from RT-qPCR, GEO meta-analysis, TCGA data mining and the integrated meta-analysis incorporating GEO microarray chips, TCGA data, in-house RT-qPCR and literature studies, miR-30d-5p expression was decreased in NSCLC tissues, and patients with NSCLC who presented with lower miR-30d-5p expression tended to display an advanced clinical progression. Significant pathways including the Mucin type O-glycan biosynthesis pathway, cell cycle pathway and cysteine and methionine metabolism pathway (all P< 0.05) revealed potential roles of the target genes of miR-30d-5p in the oncogenesis of NSCLC. Results from in vitro experiments indicated that miR-30d-5p could attenuate proliferation and viability of NSCLC cells. Among the 12 identified hub genes, nine genes including E2F3, CCNE2, SKP2, CDK6, TFDP1, LDHA, GOT2, DNMT3B and ST6GALNAC1 were validated by Pearson’s correlation test and the human protein atlas (HPA) database as targets of miR-30d-5p with higher probability. Specifically, dual luciferase reporter assay confirmed that CCNE2 was directly targeted by miR-30d-5p. Conclusion: In summary, miR-30d-5p expression is decreased in NSCLC, and it might play the role as tumor suppressor in NSCLC by regulating target genes.

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“…miR‐875‐5p regulates STAB expression to suppress the cell invasion in lung cancer (Wang et al, ). Similarly, miR‐3163 targets skp2 to modulate non‐small‐cell lung cancer cell growth (Su, Han, Wu, & Huo, ). In addition, miR‐3163 was reported to be involved in cell proliferation in retinoblastoma cancer stem cells (Jia, Wei, Liu, & Zhao, ).…”

Section: Introductionmentioning

confidence: 99%

Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

Ren

Zheng-jun

et al. 2019

Journal Cellular Physiology

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Colorectal cancer (CRC), is mostly derived from normal colon epithelial cells, and has been reported to be one of most common gastrointestinal malignancies globally. An increasing number of researchers have claimed that long noncoding RNAs (lncRNAs) exert significant functions in tumor progression. Nevertheless, the function of MAGI2-AS3 remains uncertain in CRC. The expression of MAGI2-AS3, miR-3163, and transmembrane protein 106B (TMEM106B) messenger RNA was examined by quantitative real-time polymerase chain reaction. Cell apoptosis was measured by caspase-3 activity test. Cell proliferation was tested by cell-counting kit 8 and 5-ethynyl-2′-deoxyuridine assays. Cell migration was detected by transwell assay. Western blot analysis examined the protein expression of TMEM106B. The expression of Ki-67 was evaluated by immunohistochemistry assay. The binding capacity between miR-3163 and MAGI2-AS3 (or TMEM106B) was studied by radioimmunoprecipitation and luciferase reporter assays. The expression of MAGI2-AS3 and TMEM106B was conspicuously upregulated whereas miR-3163 presented lower expression in CRC cells. MAGI2-AS3 deficiency facilitated cell apoptosis but hampered cell proliferation and migration. MAGI2-AS3 combined with miR-3163 and negatively regulated miR-3163 expression. In addition, the administration of sh-MAGI2-AS3 or miR-3163 mimics suppressed CRC cell growth in vivo. Subsequently, miR-3163 targeted TMEM106B and the transfection of sh-MAGI2-AS3 or miR-3163 mimics downregulated TMEM106B expression. Rescue assays verified that TMEM106B overexpression recovered the effects of MAGI2-AS3 inhibition on cell apoptosis, proliferation, and migration in CRC. MAGI2-AS3 drives CRC progression through regulating miR-3163/TMEM106B axis. This supplies innovative insights on the investigation of molecular mechanism in CRC progression. K E Y W O R D S CRC, MAGI2-AS3, miR-3163, TMEM106B

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Skp2 regulates non-small cell lung cancer cell growth by Meg3 and miR-3163

Cited by 62 publications

References 32 publications

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

Ginsenoside 20(S)-Rg3 Inhibits the Warburg Effect Via Modulating DNMT3A/ MiR-532-3p/HK2 Pathway in Ovarian Cancer Cells

Expression Signature and Role of miR-30d-5p in Non-Small Cell Lung Cancer: a Comprehensive Study Based on in Silico Analysis of Public Databases and in Vitro Experiments

Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

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