miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

Zhu, Xiangyu; Ma, Shenglin; Yang, Dongxiang; Liu, Yanlong; Wang, Yongpeng; Lin, Tao; Li, Yanxi; Yang, Shun Tai; Zhang, Wanchuan; Wang, Xinling

doi:10.1159/000495721

Cited by 45 publications

(32 citation statements)

References 46 publications

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“…Increasing evidence demonstrated thatcircRNAs have been found to be aberrantly expressed in various tumors and often act as miRNA sponges to regulate other oncogenes [ 24 ]. miR-142-3phas been reporteddownregulated in the primary CRC tissues, and reduced CRC tumor growth, but why CRC tumor expressed a high level of miR-142-3p is still unknown [ 25 ]. MiR-506-3p was also found downregulated in CRC tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis

et al. 2020

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Background Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Exosome shave emerged as crucial regulators of intercellular communication and that abundant Circular RNAs (circRNAs) are enriched within exosomes. CircRNAs are novel members of noncoding RNAs regulating cancer proliferation and progression. However, the function and regulatory mechanism of cancer-derived exosomal circRNAs in CRC remains unclear. Methods CRC cells-derived exosomes were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blot. CCK-8, wound healing and transwell assays, and flow cytometry assays were conducted to assess whether exosomes would affect the proliferation, metastasis, and apoptosis of CRC cells, respectively. Moreover, we performed the RNA sequencing and RT-qPCR to identify circRNAs in exosome-stimulated CRC cells. Fluorescence in situ hybridization (FISH) assay was used to detect the cellular distribution of circPACRGL. Bioinformatic analyses (StarBase 2.0) were used to pool the miRNA targets of circPACRGL. Luciferase assays were performed to verify the direct interaction. Finally, flow cytometry was used to detect the differentiation of N1-N2 neutrophils. Results Our study identified a novel CRC-derived exosomal circRNA, circPACRGL. We found circPACRGL was significantly upregulated in CRC cells after tumor-derived exosomes addition . Moreover, circPACRGL serves as a sponge for miR-142-3p/miR-506-3p to facilitate the transforming growth factor- β1 (TGF-β1) expression. As a result, circPACRGL promoted CRC cell proliferation, migration and invasion, as well as differentiation of N1 to N2 neutrophils via miR-142-3p/miR-506-3p-TGF- β1 axis. Conclusion Our study, the first to reveal that cancer-derived exosomal circPACRGL plays an oncogenic role in CRC proliferation and metastasis, providing mechanistic insights into the roles of circRNAs in CRC progression and a valuable marker for CRC treatment.

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Section: Discussionmentioning

confidence: 99%

Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis

et al. 2020

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“…Target gene prediction miRNet (https://www.mirnet.ca/), an integrated platform linking miRNAs, targets and functions, was introduced to perform miRNA's target gene prediction [33]. The miRNA-gene interactions were directly downloaded from the webpage.…”

Section: Validation Of Mirna Expressionmentioning

confidence: 99%

Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer

Ding

Yao

Fan

et al. 2020

Aging

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Background: Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as microRNA (miRNA) sponges and thus play key roles in biological processes and pathogenesis. However, studies regarding circRNAs in colorectal cancer (CRC) remain inadequate. Results: By differential expression analysis, 10 candidate circRNAs (6 upregulated and 4 downregulated circRNAs) were chosen. 9 of 10 circRNAs were available on CSCD and their structure showed the binding potential of miRNA. Intersection analysis revealed that miR-145-5p, miR-3127-5p, miR-761, miR-4766-3p, miR-135a-5p, miR-135b-5p, miR-374a-3p and miR-330-3p were 8 miRNAs with the most potential in binding circRNAs. Further expression validation and correlation analysis demonstrated hsa_circ_0001955/miR-145-5p and hsa_circ_0000977/miR-135b-5p axes as key pathways in CRC. Subsequently, target gene prediction, differential expression analysis, intersection analysis and correlation analysis showed that CDK6, MMP12 and RAB3IP were the three potential downstream targets of hsa_circ_0001955/miR-145-5p axis and FOXO1, MBNL1, MEF2C, RECK, PPM1E, TTLL7 and PCP4L1 were the seven potential downstream targets of hsa_circ_0000977/miR-135b-5p axis in CRC. Finally, we also confirmed that expression of hsa_circ_0001955 or hsa_circ_0000977 was significantly positively correlated with their individual targets in CRC. Conclusions: In the present work, we constructed a potential hsa_circ_0001955/hsa_circ_0000977-mediated circRNA-miRNA-mRNA regulatory network in CRC by a series of in silico analysis and experimental validation. Methods: Whole-transcriptome microarrays from CRC and matched normal samples were obtained from GEO. The structure of circRNA was identified by CSCD. starBase and miRNet were successively used to predict miRNA of circRNA and target gene of miRNA. Expression correlation between RNA-RNA interactions was assessed using GEO and TCGA data. Finally, a potential circRNA-miRNA-mRNA network was established based on competing endogenous RNA (ceRNA) hypothesis.

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“…MicroRNA-142-3p has been proved to fulfill an antitumor function via silencing the targeted oncogenes in a variety of cancers, such as breast cancer (Mansoori et al, 2018), hepatocellular carcinoma (Hua, Liu, Liu, & Wu, 2018), and colorectal cancer (Zhu et al, 2018). Despite being reported to sensitize NSCLC cells to chemotherarpy, the part that miR-142-3p plays in biological processes of LC cancer cells is still required to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

FUS‐induced circular RNA ZNF609 promotes tumorigenesis and progression via sponging miR‐142‐3p in lung cancer

Liu

Yang

Jiang

et al. 2020

Journal Cellular Physiology

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Circular RNAs (circRNAs) have been associated with lung cancer (LC), one of the most common cancers, but the underlying molecular mechanisms of the specific correlation with LC carcinogenesis remain unveiled. Quantitative real-time polymerase chain reaction was applied to examine the level of circZNF609. LC cells were transfected with silenced circZNF609 by siRNAs, and cell proliferation, migration, and apoptosis were evaluated to reflect the influences of circZNF609 knockdown in LC. Biotincoupled circRNA capture, FISH and luciferase reporter assays were performed to study the relationship between circZNF609 and miR-142-3p. In current work, it was discovered that circZNF609 functioned as an onco-circRNA, which exhibited high expression as well as facilitated the proliferation and migration in LC cells. Next, we discovered that FUS RNA-binding protein, which could bind to the ZNF609 pre-mRNA, induced circZNF609 formation, and increased circZNF609 expression in LC. Furthermore, circZNF609 was verified to sponge and sequester miR-142-3p; circZNF609 enhanced LC cell proliferative and migrative ability via targeting miR-142-3p. Finally, G protein subunit beta 2 (GNB2) was figured out to involve in circZNF609/miR-142-3p axis-induced LC development. Conclusively, the results indicated that FUS-induced circZNF609 exerts promotional effects on LC cell proliferation and migration through modulation of the miR-142-3p/GNB2 axis, which could offer new insight for understanding LC.

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miR-142-3p Suppresses Cell Growth by Targeting CDK4 in Colorectal Cancer

Cited by 45 publications

References 46 publications

Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis

Exosomal circPACRGL promotes progression of colorectal cancer via the miR-142-3p/miR-506-3p- TGF-β1 axis

Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer

FUS‐induced circular RNA ZNF609 promotes tumorigenesis and progression via sponging miR‐142‐3p in lung cancer

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