Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug Sunitinib in Glioblastoma

Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Huo, Lei; Liu, Jinfang; Lu, Jinmiao

doi:10.1007/s12013-014-0501-8

Cited by 17 publications

(20 citation statements)

References 38 publications

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“…[39][40][41][42][43] Correlation analyses between genome-wide miRNA expression and BCRP/ABCG2 protein expression in ccRCC patients of Cohort 2 did not reveal any significant association. [39][40][41][42][43] Correlation analyses between genome-wide miRNA expression and BCRP/ABCG2 protein expression in ccRCC patients of Cohort 2 did not reveal any significant association.…”

Section: Discussionmentioning

confidence: 85%

Characterization of the breast cancer resistance protein (BCRP/ABCG2) in clear cell renal cell carcinoma

Reustle

Fisel

Renner

et al. 2018

Intl Journal of Cancer

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The efflux transporter breast cancer resistance protein BCRP/ABCG2 is well-known for its contribution to multi-drug resistance in cancer. Its relevance in cancer biology independent from drug efflux remains largely elusive. Our study aimed at elucidating the biological relevance and regulatory mechanisms of BCRP/ABCG2 in clear cell renal cell carcinoma (ccRCC) and disease progression. Two independent ccRCC-cohorts [Cohort 1 (KIRC/TCGA): n = 453, Cohort 2: n = 64] were investigated to elucidate BCRP/ABCG2 mRNA and protein expression and their association with survival. The impact of BCRP/ABCG2 on response to sunitinib treatment was investigated in two independent sunitinib-treated ccRCC-cohorts based on mRNA levels. Moreover, underlying regulatory mechanisms for interindividual variability of BCRP/ABCG2 expression were systematically assessed. Owing to redundant functional properties, mRNA and protein expression of the multidrug resistance protein MDR1/ABCB1 were additionally evaluated in these cohorts. In independent ccRCC-cohorts, low BCRP/ABCG2 and MDR1/ABCB1 mRNA and protein expression were associated with severity (e.g., tumor stage) of ccRCC and poor cancer-specific survival. BCRP/ABCG2 and MDR1/ABCB1 mRNA expression were linked to decreased progression-free survival after sunitinib treatment. Germline and somatic variants influenced interindividual variability of BCRP/ABCG2 expression only moderately. miR-212-3p and miR-132-3p were identified to regulate BCRP/ABCG2 posttranscriptionally by interaction with the ABCG2 3'UTR as confirmed through reporter gene assays in RCC cell lines. In summary, BCRP/ABCG2 expression in ccRCC underlies considerable interindividual variability with impact on patient survival and response to sunitinib treatment. While germline or somatic genetic variants and DNA methylation cannot explain aberrant BCRP/ABCG2 expression, miR-212-3p and miR-132-3p were identified to contribute to posttranscriptional regulation of BCRP/ABCG2.

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Section: Discussionmentioning

confidence: 85%

Characterization of the breast cancer resistance protein (BCRP/ABCG2) in clear cell renal cell carcinoma

Reustle

Fisel

Renner

et al. 2018

Intl Journal of Cancer

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“…A similar example of the power of combining miRNA-based therapy with anti-angiogenic agents was shown in a study by Liu et al Here, miR-145 mimics were combined with sunitinib on U87 cells which showed additive effects, even though very high concentrations of sunitinib were used [74]. It must be noted, however, that both studies only addressed tumor cell biology and not inasmuch tumor angiogenesis.…”

Section: Anti-angiogenic Mirna-based Combination Therapymentioning

confidence: 83%

miRNAs: micro-managers of anticancer combination therapies

et al. 2017

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Angiogenesis is one of the hallmarks of cancer progression and as such has been considered a target of therapeutic interest. However, single targeted agents have not fully lived up to the initial promise of anti-angiogenic therapy. Therefore, it has been suggested that combining therapies and agents will be the way forward in the oncology field. In recent years, microRNAs (miRNAs) have received considerable attention as drivers of tumor development and progression, either acting as tumor suppressors or as oncogenes (so-called oncomiRs), as well as in the process of tumor angiogenesis (angiomiRs). Not only from a functional, but also from a therapeutic view, miRNAs are attractive tools. Thus far, several mimics and antagonists of miRNAs have entered clinical development. Here, we review the provenance and promise of miRNAs as targets as well as therapeutics to contribute to anti-angiogenesis-based (combination) treatment of cancer.

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“…Since miR‐145 has been identified as an inhibitor of BCRP and P‐gp (Liu et al, b), the effect of TGF‐β1 on miR‐145 expression were examined in HepG2 cells. The results showed that TGF‐β1 markedly downregulated miR‐145 expression in HepG2 cells (Figure a).…”

Section: Resultsmentioning

confidence: 99%

“…Our results showed that TGF‐β1 upregulated HOTAIR expression through SMAD4, and the upregulation of HOTAIR reduced miR‐145 expression through the HOTAIR/PRC2 pathway. miR‐145 inhibited P‐gp and BCRP expression (Liu et al, a), while miR‐145 inhibitor upregulated the expression of P‐gp and BCRP. P‐gp and/or BCRP overexpression enhanced drug efflux transport in hepatocellular carcinoma cells, resulting in a decrease of intracellular drug concentration.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, miR‐181a, miR‐487a, miR‐328 and miR‐520 h have been identified to inhibit the expression of BCRP by targeting the BCRP 3′‐UTR (Jiao et al, ; Ma et al, ; Pan, Morris, & Yu, ; Wang et al, ). miR‐145 has been identified to be downregulated in a variety of tumors, such as prostate cancer, colorectal cancer and bladder cancer (Ozen et al, ; Tan, Qiu, Li, & Liang, ; Yamada et al, ), and is a direct inhibitor of BCRP and P‐gp (Liu et al, a). It is well known that MDR causes chemotherapy failure, which is associated with a decrease in drug concentration in cancer cells, usually due to overexpression of ABC transporters including P‐gp and BCRP.…”

Section: Discussionmentioning

confidence: 99%

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TGF‐β1 elevates P‐gp and BCRP in hepatocellular carcinoma through HOTAIR/miR‐145 axis

Kong

Qiu

et al. 2019

Biopharm & Drug Disp

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Multidrug resistance (MDR) is common in patients and has been linked to transforming growth factor‐β1 (TGF‐β1) and overexpression of drug efflux transporters P‐glycoprotein (P‐gp) and breast cancer resistance protein (BCRP), although the molecular mechanisms remain largely unknown. This study aimed to investigate the mechanisms underlying TGF‐β1‐induced MDR in hepatocellular carcinoma (HCC) cells. It was found that TGF‐β1 upregulated HOX transcript antisense RNA (HOTAIR) expression in HCC cells. When drosophila mothers against decapentaplegic 4 (SMAD4) was silenced, HOTAIR expression was accordingly reduced. Meanwhile, miR‐145 expression was increased in the case HOTAIR was silenced. If the enhancer of zeste homolog 2 (EZH2) was knocked down using small interfering RNA (siRNA), miR‐145 expression was decreased. Then, the regulatory role of miR‐145 in P‐gp and BCRP expression was explored. The results showed that the expression of P‐gp and BCRP protein was suppressed by miR‐145 through binding to the 3′‐untranslated regions (3′‐UTRs) of P‐gp and BCRP. In conclusion, our study revealed a novel mechanism explaining TGF‐β1‐induced MDR in HCC through upregulating P‐gp and BCRP via the SMAD4/HOTAIR/miR‐145 axis.

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Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug Sunitinib in Glioblastoma

Cited by 17 publications

References 38 publications

Characterization of the breast cancer resistance protein (BCRP/ABCG2) in clear cell renal cell carcinoma

Characterization of the breast cancer resistance protein (BCRP/ABCG2) in clear cell renal cell carcinoma

miRNAs: micro-managers of anticancer combination therapies

TGF‐β1 elevates P‐gp and BCRP in hepatocellular carcinoma through HOTAIR/miR‐145 axis

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