MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma

Liu, Wenjuan; Li, Honghong; Wang, Yan; Zhao, Xinyao; Guo, Yuanying; Jin, Jing; Chi, Rongxiang

doi:10.1016/j.gene.2017.05.040

Cited by 47 publications

(45 citation statements)

References 22 publications

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“…miRNAs regulate the expression of target genes via association with the complementary sites of 3'-UTR region of mRNAs (5). Large numbers of studies indicate that miRNAs serve as important regulators in diverse biological processes, including cell survival, apoptosis and metastasis (6,7). Therefore, miRNA expression is closely correlated with tumor development.…”

Section: Introductionmentioning

confidence: 99%

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

Liu

Sun

et al. 2018

Mol Med Report

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MicroRNA (miR)‑30a‑5p has been reported to suppress the progression of hepatocellular cancer, renal cell carcinoma, oral cancer and gastric cancer. However, whether miR‑30a‑5p is involved in the regulation of melanoma remains unclear. The present study revealed that miR‑30a‑5p was downregulated in melanoma tissues and cell lines. Overexpression of miR‑30a‑5p significantly inhibited the proliferation, migration and invasion of melanoma cells in vitro. In addition, ectopic expression of miR‑30a‑5p delayed tumor growth in vivo. In terms of mechanism, miR‑30a‑5p targeted sex determining region Y‑box 4 (SOX4) and impeded the expression of SOX4 in melanoma cells. In addition, SOX4 was upregulated in melanoma tissues and cell lines when compared with normal tissues or cells. Furthermore, overexpression of SOX4 significantly rescued the proliferation, migration and invasion of melanoma cells transfected with miR‑30a‑5p mimics. Taken together, the results of the present study demonstrated that miR‑30a‑5p suppressed the proliferation, migration and invasion of melanoma cells in SOX4‑dependent manner.

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Section: Introductionmentioning

confidence: 99%

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

Liu

Sun

et al. 2018

Mol Med Report

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“…However, one should remember that specific miRNAs can simultaneously produce competing oncogenic and tumor suppressive effects and an overall net oncogenic or net tumor-suppressive effect of miRNA may depend on the balance between miRNA-mediated upregulation or downregulation of oncogenic and tumor-suppressive pathways, the effects of the miRNA on cancer-immune system interactions and a plethora of other tumor-modifying extrinsic factors [51] . Most of upregulated miRNAs in DNMT2-silenced fibroblasts have been reported to suppress cell proliferation and promote multiple antitumor effects in different cancer models [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] . For example, miR-28-5p inhibited proliferation and migration by directly inhibiting RAP1B, a Ras-related small GTP-binding oncoprotein, in renal cell carcinoma [52] ; miR-34a-3p reduced the proliferation of meningioma cells by targeting SMAD4, FRAT1 and BCL2 [54] ; miR-30b-5p limited cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma [55] and miR-30b-5p repressed cell proliferation by targeting DNMT3A in hepatocellular carcinoma [56] ; miR-409-3p inhibited gastric cancer cell proliferation and promoted apoptosis by targeting the transcriptional regulator PHF10 [61] and miR-409-3p suppressed breast cancer cell growth and invasion by targeting Akt1 [62] .…”

Section: Discussionmentioning

confidence: 99%

Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression

et al. 2018

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Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation. DNMT2 silencing promoted upregulation of proliferation-related and tumor suppressor miRNAs, namely miR-28-3p, miR-34a-3p, miR-30b-5p, miR-29b-3p, miR-200c-3p, miR-28-5p, miR-379-5p, miR-382-5p, miR-194-5p, miR-193b-3p and miR-409-3p. Moreover, DNMT2 silencing induced cellular senescence and DNMT2 levels were elevated in replicatively senescent cells. Taken together, we found that DNMT2 may take part in the regulation of cell proliferation and longevity in human fibroblasts and speculate that the manipulation of DNMT2 levels that limits cell proliferation may be potentially useful anticancer strategy.

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“…Interestingly, miR‐30a has also been shown to serve as both oncogene or onco‐suppressor in different cancer types . Apart from miR‐30a, miR‐30b‐5p functions as a tumor suppressor in renal cell carcinoma by inhibiting EMT, cell proliferationand metastasis . Given the potentially conflicting effects of the miR‐30 family on oncogenesis and the fact that the miR‐30‐5p mature strand has not been extensively explored in CRC, we decided to investigate the effects of miR‐30‐5p family members on CRC stemness and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

MiR‐30‐5p suppresses cell chemoresistance and stemness in colorectal cancer through USP22/Wnt/β‐catenin signaling axis

Jiang

Miao

Wang

et al. 2018

J Cellular Molecular Medi

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Colorectal cancer (CRC) remains both common and fatal, and its successful treatment is greatly limited by the development of stem cell‐like characteristics (stemness) and chemoresistance. MiR‐30‐5p has been shown to function as a tumor suppressor by targeting the Wnt/β‐catenin signaling pathway, but its activity in CRC has never been assessed. We hypothesized that miR‐30‐5p exerts anti‐oncogenic effects in CRC by regulating the USP22/Wnt/β‐catenin signaling axis. In the present study, we demonstrate that tissues from CRC patients and human CRC cell lines show significantly decreased miR‐30‐5p family expression. After identifying the 3’UTR of USP22 as a potential binding site of miR‐30‐5p, we constructed a luciferase reporter containing the potential miR‐30‐5p binding site and measured the effects on USP22 expression. Western blot assays showed that miR‐30‐5p decreased USP22 protein expression in HEK293 and Caco2 CRC cells. To evaluate the effects of miR‐30‐5p on CRC cell stemness, we isolated CD133 + CRC cells (Caco2 and HCT15). We then determined that, while miR‐30‐5p is normally decreased in CD133 + CRC cells, miR‐30‐5p overexpression significantly reduces expression of stem cell markers CD133 and Sox2, sphere formation, and cell proliferation. Similarly, we found that miR‐30‐5p expression is normally reduced in 5‐fluorouracil (5‐FU) resistant CRC cells, whereas miR‐30‐5p overexpression in 5‐FU resistant cells reduces sphere formation and cell viability. Inhibition of miR‐30‐5p reversed the process. Finally, we determined that miR‐30‐5p attenuates the expression of Wnt/β‐catenin signaling target genes (Axin2 and MYC), Wnt luciferase activity, and β‐catenin protein levels in CRC stem cells.

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MiR-30b-5p functions as a tumor suppressor in cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma

Cited by 47 publications

References 22 publications

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression

MiR‐30‐5p suppresses cell chemoresistance and stemness in colorectal cancer through USP22/Wnt/β‐catenin signaling axis

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