Dicer suppresses cytoskeleton remodeling and tumorigenesis of colorectal epithelium by miR-324-5p mediated suppression of HMGXB3 and WASF-2

Sun, Li; Xing, Cheng; Zheng, Zhi-Ming; Liu, Yao; Chen, Liangyan; Shen, Tong; Zhou, Qun; Liu, Yu Hong; Gan, Wen Juan; Wang, Jingru; Xu, Yong; Li, Jian Ming

doi:10.18632/oncotarget.18218

Cited by 15 publications

(15 citation statements)

References 42 publications

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“…Emerging evidence indicates that microRNAs participate in many physiological and pathological processes [ 16 – 18 ]. miR-324-5p, a novel cancer-related miRNA, was dysregulated in many tumors [ 19 – 22 ]. miR-324-5p inhibits HCC invasion by counteracting ECM degradation through regulating ETS1 and SP1 [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p

Jiang

Huang

Zhao

et al. 2018

J Exp Clin Cancer Res

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BackgroundIncreasing studies confirmed that abnormal lncRNAs expression play a critical role in cervical cancer (CC) development and progression. LncRNA TPT1-AS1, a novel lncRNA, its role and underlying mechanisms involved in CC remain largely unknown.MethodsColony formation, EdU and Transwell assays were used to determine colony formation, proliferation, migration and invasion in vitro. The subcutaneous tumor model and tail vein injection lung metastasis model were performed to check tumor growth and metastasis in vivo. Luciferase activity and RIP experiment were carried out to determine the interaction between miR-324-5p and TPT1-AS1.ResultsWe demonstrated for the first time that TPT1-AS1 expression was up-regulated in CC tissues and cell lines. High TPT1-AS1 was significantly correlated with adverse prognostic characteristics and poor survival. TPT1-AS1 overexpression and knockdown experiments revealed that TPT1-AS1 promoted cell colony formation, proliferation, migration, invasion and EMT progression of CC cells in vitro and in vivo. The underlying mechanism indicated that TPT1-AS1 functioned as an endogenous sponge for miR-324-5p in CC cells. Gain- and loss- experiment confirmed that miR-324-5p inhibited cell colony formation, proliferation, migration, invasion and EMT progression of CC cells, and mediated the biological effects of TPT1-AS1. Further investigations confirmed that SP1 was a direct target of miR-324-5p and mediated the effects of TPT1-AS1 and miR-324-5p in CC.ConclusionsWe demonstrated for the first time that TPT1-AS1 as an oncogenic lncRNA in CC progression and as a potential target for CC cure.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0846-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p

Jiang

Huang

Zhao

et al. 2018

J Exp Clin Cancer Res

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“…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%

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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“…Thus, further clarification is needed regarding the miRNAs acting in the intestinal compartment, along with their target genes and the regulatory networks that are affected. Tissue specific Dicer KO models have been used in some studies to assess the importance of miRNAs in intestinal homeostasis [15][16][17][18] , as well as their involvement in lipid metabolism [19][20][21] . While the primary role of miRNAs seems to be the 'fine-tuning' of gene expression, it is under conditions of stress that the functions of miRNAs become especially pronounced, underscoring their roles in disease 22 .…”

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confidence: 99%

Intestinal miRNAs regulated in response to dietary lipids

Gil-Zamorano

Tomé‐Carneiro

Hazas

et al. 2020

Sci Rep

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The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation. According to our results, changes in miRNA expression in response to fat ingestion are dependent on factors such as time upon exposure, gender and small intestine section. Classic and recent intestinal in vitro models (i.e. differentiated Caco-2 cells and murine organoids) partially mirror miRNA modulation in response to lipid challenges in vivo. Moreover, intestinal miRNAs might play a role in triglyceride absorption and produce changes in lipid accumulation in intestinal tissues as seen in a generated intestinal Dicer1-deletion murine model. Overall, despite some variability between the different experimental cohorts and in vitro models, results show that some miRNAs analysed here are modulated in response to dietary lipids, hence likely to participate in the regulation of lipid metabolism, and call for further research.

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Dicer suppresses cytoskeleton remodeling and tumorigenesis of colorectal epithelium by miR-324-5p mediated suppression of HMGXB3 and WASF-2

Cited by 15 publications

References 42 publications

RETRACTED ARTICLE: Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p

RETRACTED ARTICLE: Long non-coding RNA TPT1-AS1 promotes cell growth and metastasis in cervical cancer via acting AS a sponge for miR-324-5p

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

Intestinal miRNAs regulated in response to dietary lipids

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