Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both<i>In Vitro</i>and<i>In Vivo</i>

Zeng, Xingruo; Zhou, Xu; Gu, Jiayan; Huang, Haishan; Gao, Guangxun; Zhang, Xiaoru; Li, Jingxia; Jin, Honglei; Jiang, Guosong; Sun, Hong; Huang, Chuanshu

doi:10.1158/1535-7163.mct-15-0606

Cited by 39 publications

(59 citation statements)

References 51 publications

(72 reference statements)

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“…It has been shown that Sp1 acts as a tumor suppressor to suppress colorectal cancer growth and metastasis by increasing miRNA‐52d‐5p transcription for target CTHRC1 (Yan et al ., ). We have reported that the anti‐cancer drug ISO downregulates Sp1 translation to block BC cell growth and IHC‐P results show Sp1 is upregulated in BBN‐induced BC tissues, suggesting an oncogenic role of Sp1 in BC (Zeng et al ., ). Here, we further reveal that Sp1 bound directly to the mmp‐2 promoter and increased its transcription, promoting bladder cancer cell invasion.…”

Section: Discussionmentioning

confidence: 97%

RhoGDIβ promotes Sp1/MMP‐2 expression and bladder cancer invasion through perturbing miR‐200c‐targeted JNK2 protein translation

et al. 2017

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Our most recent studies demonstrate that RhoGDIβ is able to promote human bladder cancer (BC) invasion and metastasis in an X‐link inhibitor of apoptosis protein‐dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)‐2 protein expression. We also found that RhoGDIβ and MMP‐2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIβ inhibited MMP‐2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIβ upregulated MMP‐2 protein expression and promoted invasion as well. The mechanistic studies indicated that MMP‐2 was upregulated by RhoGDIβ at the transcriptional level by increased specific binding of the transcription factor Sp1 to the mmp‐2 promoter region. Further investigation revealed that RhoGDIβ overexpression led to downregulation of miR‐200c, whereas miR‐200c was able directly to target 3′‐UTR of jnk2 mRNA and attenuated JNK2 protein translation, which resulted in attenuation of Sp1 mRNA and protein expression in turn, inhibiting Sp1‐dependent mmp‐2 transcription. Collectively, our studies demonstrate that RhoGDIβ overexpression inhibits miR‐200c abundance, which consequently results in increases of JNK2 protein translation, Sp1 expression, mmp‐2 transcription, and BC invasion. These findings, together with our previous results showing X‐link inhibitor of apoptosis protein mediating mRNA stabilization of both RhoGDIβ and mmp‐2, reveal the nature of the MMP‐2 regulatory network, which leads to MMP‐2 overexpression and BC invasion.

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Section: Discussionmentioning

confidence: 97%

RhoGDIβ promotes Sp1/MMP‐2 expression and bladder cancer invasion through perturbing miR‐200c‐targeted JNK2 protein translation

et al. 2017

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“…The total cell microRNAs and human bladder tissue microRNAs were extracted using the miRNeasy Mini Kit (Qiagen, Valencia, CA, USA) as described in our previous studies [45,46]. Total RNA (1 μg) was used for reverse transcription, and analysis of miR-7, miR-17, miR-23a, miR-24, miR-93, miR-129, miR-137, miR-200c, and miR-214 expression were determined by the 7900HT Fast Real-time PCR system (Applied Biosystems, Carlsbad, CA, USA) using the miScript PCR kit (Qiagen, Valencia, CA, USA).…”

Section: Quantitative Rt-pcr For Mirna Assaymentioning

confidence: 99%

“…The control inserts without Matrigel and invasion kit were purchased from BD Falcon; the invasion assay was performed according to the manufacturer's instruction in normal cell culture serum as described in our previous studies [18,45]. The cells were seeded in the inserts both with and without Matrigel.…”

Section: Cell Migration and Invasion Assaymentioning

confidence: 99%

Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer

Jin

Xue

et al. 2019

Cell Adhesion & Migration

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Our previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs. Mechanistic studies indicated that XIAP overexpression in the highly metastatic T24T cells was due to increased mRNA stability of XIAP that was mediated by downregulated miR-200c. Moreover, the downregulated miR-200c was due to CREB inactivation, while miR-200c downregulation reduced its binding to the 3’-UTR region of XIAP mRNA. Collectively, our results demonstrate the molecular basis leading to XIAP overexpression and its crucial role in BC invasion.

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“…Several studies have shown that among the potential causes for BC, there are a variety of molecular factors such as noncoding RNAs (10)(11)(12)(13)(14)(15). Included in the latter are microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene protein expression by repressing protein translation or by affecting mRNA stability through binding to its specific target sequences.…”

mentioning

confidence: 99%

“…A growing collection of evidence has demonstrated that miRNAs play important roles in regulating growth and invasion, as well as chemo-sensitivity of different types of cancers. Several miRNAs have been verified as contributing to BC cell metastasis and proliferation (10)(11)(12)(13). However, precise mechanisms underlying how these miRNAs act in BC are poorly defined.…”

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confidence: 99%

Inhibition of UBE2N‐dependent CDK6 protein degradation by miR‐934 promotes human bladder cancer cell growth

Huang¹,

Ren²,

Lin

et al. 2019

The FASEB Journal

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Because bladder cancer (BC) is one of the most common malignant cancers of the urinary system, identification of BC cell growth‐associated effectors is of great significance. Cyclin‐dependent kinase (CDK)6 is a member of the CDK family of cell cycle‐related proteins and plays an important role in cancer cell growth. This is borne out by the fact that a CDK6 inhibitor had been approved to treat several types of cancers. Nevertheless, underlying molecular mechanisms concerning how to regulate CDK6 expression in BC remains unclear. In the present study, it was observed that miR‐934 was much higher in human BCs and human BC cell lines as well. The results also revealed that miR‐934 inhibition dramatically decreased human BC cell monolayer growth in vitro and xenograft tumor growth in vivo; the outcomes were accompanied by CDK6 protein down‐regulation and G0‐G1 cell cycle arrest. Moreover, overexpression of CDK6 reversed the inhibition of BC cell growth induced by miR‐934. Further studies showed that miR‐934 binds to a 3'‐UTR of ubiquitin‐conjugating enzyme 2N (ube2n) mRNA, down‐regulated UBE2N protein expression; this, in turn, attenuated CDK6 protein degradation and led to CDK6 protein accumulation as well as the promotion of BC tumor growth. Collectively, this study not only establishes a novel regulatory axis of miR‐934/UBE2N of CDK6 but also provides data suggesting that miR‐934 and UBE2N may be potentially promising targets for therapeutic strategies against BC.—Yan, H., Ren, S., Lin, Q., Yu, Y., Chen, C., Hua, X., Jin, H., Lu, Y., Zhang, H., Xie, Q., Huang, C., Huang, H. Inhibition of UBE2N‐dependent CDK6 protein degradation by miR‐934 promotes human bladder cancer cell growth. FASEB J. 33, 12112‐12123 (2019). http://www.fasebj.org

show abstract

Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity BothIn VitroandIn Vivo

Cited by 39 publications

References 51 publications

RhoGDIβ promotes Sp1/MMP‐2 expression and bladder cancer invasion through perturbing miR‐200c‐targeted JNK2 protein translation

RhoGDIβ promotes Sp1/MMP‐2 expression and bladder cancer invasion through perturbing miR‐200c‐targeted JNK2 protein translation

Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer

Inhibition of UBE2N‐dependent CDK6 protein degradation by miR‐934 promotes human bladder cancer cell growth

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