miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy

Yin, Wang; Nie, Yuehua; Zhang, Zhiwei; Xie, Liping; He, Xiu‐Sheng

doi:10.3892/or.2015.3996

Cited by 37 publications

(21 citation statements)

References 26 publications

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“…Several of the differentially expressed miRNAs identified here were previously shown to be involved in diverse stress responses including apoptosis and senescence, further validating the specificity of our screen [ 16 , 29 , 38 – 40 ]. For the following reasons we focused our attention mainly on the function of miR-30e.…”

Section: Discussionsupporting

confidence: 81%

miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3

et al. 2016

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MicroRNAs (miRNAs), a class of small non-coding RNAs that usually cause gene silencing by translational repression or degradation of mRNAs, are implicated in DNA damage-induced stress responses. To identify senescence-associated miRNAs, we performed microarray analyses using wild-type and p53-deficient HCT116 colon carcinoma cells that following gamma-irradiation (γIR) are driven into senescence and apoptosis, respectively. Several miRNAs including miR-30e were found upregulated in a p53-dependent manner specifically in senescent cells, but not in apoptotic cells. Overexpression of miR-30e in HCT116 cells not only inhibited γIR-, etoposide- or miR-34a-induced caspase-3-like DEVDase activities and cell death, but greatly accelerated and augmented their senescent phenotype. Consistently, procaspase-3 protein, but not mRNA decreased in the presence of miR-30e, whereas expression of the cyclin-dependent kinase inhibitor p21 increased both at the mRNA and protein level. Performing luciferase reporter gene assays, we identified the 3′-UTR of the caspase-3 mRNA as a direct miR-30e target. In contrast, although miR-30e was unable to bind to the p21 mRNA, it increased expression of a luciferase construct containing the p21 promoter, suggesting that the miR-30e-mediated upregulation of p21 occurs indirectly at the transcriptional level. Interestingly, despite suppressing procaspase-3 expression, miR-30e was unable to protect RKO colon carcinoma cells from DNA damage-induced death or to induce senescence, as miR-30e completely fails to upregulate p21 in these cells. These data suggest that miR-30e functions in a cell type-dependent manner as an important molecular switch for DNA damage-induced stress responses and may thus represent a target of therapeutic value.

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Section: Discussionsupporting

confidence: 81%

miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3

et al. 2016

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“…MiR-193b was found to be downregulated in hepatocellular carcinoma. Enforced expression of miR-193b significantly enhanced the curative effect of cisplatin 26 . Combination treatment with tamoxifen and anti-miR-181b or anti-miR-221 proved to reduce breast tumor size 27 .…”

Section: Discussionmentioning

confidence: 96%

MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma

Sun

Dong

et al. 2016

Sci Rep

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Emerging evidence shows that microRNAs (miRNAs) act as critical regulators in the progression and chemoresistance of multiple tumors, including osteosarcoma (OS). In this study, we found that the level of miR-24 was increased in OS patients’ serum, tumor tissues and OS cell lines. Furthermore, we found that knockdown of miR-24 by its specific inhibitors significantly increased the therapeutic effect of doxorubicin (DOX) on OS cell lines (MG-63 and HOS). Moreover, miR-24 inhibitors resensitized the doxorubicin-resistant MG-63 cells (MG-63/R) and HOS cells (HOS/R) to DOX. As the gene of Bcl-2 interacting mediator of cell death (BIM) was proved to be a target of miR-24 in MG-63/R cells, we further observed that the miR-24 inhibitors promoted the DOX-induced apoptosis via mitochondrial pathway. In addition, results of immunoprecipitation showed the release of second mitochondria derived activator of caspase/ direct IAP binding protein with low pI (Smac/DIABLO) abolished the biological activity of X-linked inhibitor of apoptosis protein (XIAP) by binding with it, which subsequently induced the activation of caspase 9, 7 and 3. In summary, those results strongly suggest that the miR-24-BIM-Smac/DIABLO axis might be a novel target for the treatment of OS.

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“…In addition, plenty of researches showed that the expression level of MCL-1 determines the sensitivity of multiple cancers to cisplatin. For instance, microRNA-193b enhances the cytotoxicity of cisplatin to hepatocellular carcinoma cells by targeting Mcl-1 [13]. Imperatorin acts as a cisplatin sensitizer via down-regulating MCL-1 expression in HCC chemotherapy [14].…”

Section: Introductionmentioning

confidence: 99%

Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis

Xia

et al. 2017

BMC Cancer

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BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed.MethodsWe used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin.ResultsThe present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage.ConclusionsThe current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression.

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miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy

Cited by 37 publications

References 26 publications

miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3

miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3

MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma

Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis

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