Overexpression of the microRNA miR‐433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells

Weiner-Gorzel, Karolina; Dempsey, Eugene; Milewska, Małgorzata; McGoldrick, Aloysius; Toh, Valerie; Walsh, Aoibheann; Lindsay, Sinéad; Gubbins, Luke; Cannon, Aoife; Sharpe, Daniel; O'Sullivan, Jacintha; Murphy, Madeline; Madden, Stephen F.; Kell, Malcolm R.; McCann, Amanda; Furlong, Fiona

doi:10.1002/cam4.409

Cited by 139 publications

(101 citation statements)

References 49 publications

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“…The present data, along with an analysis of a published dataset (27), showed that miR-433 was overexpressed in osteosarcoma tissues and cell lines. In combi nation with previous reports revealing the roles of miR-433 in various other types of cancer, including ovarian and gastric cancer (28,29), the present study further confirmed that miR-433 functions as an oncomiR in osteosarcoma. Furthermore, overexpression of miR-433 was shown to decrease the apoptosis of osteosarcoma cells by targeting PDCD4 in vitro.…”

Section: Discussionsupporting

confidence: 89%

MicroRNA-433 regulates apoptosis by targeting PDCD4 in human osteosarcoma cells

Sun

Wang

et al. 2017

Oncology Letters

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Abstract. Osteosarcoma is the most common aggressive sarcoma of the bone in children and adolescents. It is characterized by a high level of genetic instability and recurrent DNA deletions and amplifications. microRNAs (miRNAs) play a key role in cancer initiation, progression and metastasis; however, the potential role of miRNAs in osteosarcoma remains largely unknown. In the present study, miR-433 was shown to be overexpressed in osteosarcoma tissues compared with normal human osteoblasts. Transfection of miR-433 mimics into osteosarcoma cell lines significantly decreased apoptosis by targeting programmed cell death 4, a tumor suppressor that is involved in apoptosis. In contrast, inhibition of miR-433 enhanced apoptosis. Furthermore, in vivo miR-433 overexpression inhibited the apoptosis of tumor cells and increased tumor growth. The results of the present study suggested that miR-433 is a potential molecular target for osteosarcoma therapy.

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Section: Discussionsupporting

confidence: 89%

MicroRNA-433 regulates apoptosis by targeting PDCD4 in human osteosarcoma cells

Sun

Wang

et al. 2017

Oncology Letters

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“…Expression of miR-433 was normalized using U6 RNA (for RNA from cells and tissues) and with Caenorhabditis elegans miR-39 mimic (for RNA from culture supernatant and serum samples) which was used as an RNA spike-in. Specific primers for miR-433, U6 and C. elegans miR-39 RNA were obtained from RiboBio (15,19). In total, three individual experiments were performed.…”

Section: Reverse Transcription-quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…miR-433 has been identified as a cancer-associated miRNA in various types of tumor, including bladder cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma and oral squamous cell carcinoma (13-17). Furthermore, aberrant expression levels of miR-433 have been identified to be associated with chemosensitivity and enhanced survival of ovarian cancer cells (15,18).In the present study, gemcitabine-resistant (GR) subclones were established on the basis of stable transfectants of CDK10 or cyclin M overexpression. To provide a possible mechanism for cyclin M downregulation in acquired chemoresistance of gallbladder cancer cells, miR-433 was predicted to target cyclin M. Furthermore, the association of serum levels of miR-433 and the chemotherapeutic response in gallbladder cancer was evaluated.…”

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confidence: 98%

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miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

Zhang

et al. 2017

Oncol Lett

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Abstract. Resistance to chemotherapy is associated with dismal prognosis in patients with gallbladder cancer. Cyclin-dependent kinase 10 (CDK10) influences the chemosensitivity of gallbladder cancer cells, and cyclin M is the activating factor and binding partner of CDK10. To determine the effect of CDK10 or cyclin M overexpression on chemosensitivity, gemcitabine-resistant (GR) subclones were established from CDK10 or cyclin M stable transfectants. Stable overexpression of CDK10 increased the sensitivity to gemcitabine in non-resistant cells and did not further increase the sensitivity to gemcitabine in the GR subclones. GR subclones exhibited a significantly decreased expression of cyclin M while maintaining the expression levels of CDK10, compared with the non-resistant cells. MicroRNA (miR)-433 was identified as a candidate factor involved in the mechanism of the downregulation of M cyclin in GR subclones. Luciferase assays confirmed the interaction between miR-433 and the 3' untranslated region (3'UTR) of cyclin M. Additionally, ectopic expression of miR-433 significantly decreased the expression of cyclin M. Finally, increased expression of circulating miR-433 was associated with poor outcome of chemotherapy. The results of the present study suggest that miR-433 is a potential biomarker for evaluating chemosensitivity in gallbladder cancer. IntroductionGallbladder cancer is a relatively rare disease, with an estimated annual incidence of between 2 and 3 individuals/100,000; however, it is the most frequently encountered malignancy of the biliary tract (1,2). Complete surgical resection is the only potentially curative approach in early stages of the disease; however, the majority of cases are diagnosed in advanced stages. Additionally, because the aggressive malignancy tolerates traditional chemotherapy and radiotherapy, these cases have a dismal prognosis with an overall 5-year survival rate of <5% (3). Therefore, improving the diagnostic accuracy during the early stages and identifying the molecular mechanisms associated with chemotherapy or radiation resistance may provide a potential therapeutic approach for the treatment of gallbladder cancer.Cyclin M, also known as FAM58A, is a member of the cyclin family, which serves important regulatory functions in the cell cycle and transcription (4). Mutations in cyclin M cause toe syndactyly, telecanthus and anogenital and renal malformations syndrome, a human developmental anomaly (4,5). However, the function of cyclin M in other diseases remains unclear. Cyclin M has been identified as the binding partner for cyclin-dependent kinase 10 (CDK10) (5). CDK10 is involved in the regulation of cell division and function in various types of tumor (6-10). It was confirmed that CDK10 functions as a tumor suppressor gene and regulates the survivability of biliary tract cancer cells, including gallbladder cancer cells (8). These results suggest that cyclin M may also be involved in cancer development through binding to CDK10.MicroRNAs (miRNAs) are key negative regulator...

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“…Numerous studies have demonstrated that miRNAs can perform oncogenic or tumor suppressive roles in various types of cancers. Previous studies have demonstrated the functional roles of miR-433 in several types of cancer, including retinoblastoma (10), ovarian cancer (11), bladder cancer (11), oral squamous cell carcinoma (OSCC) (12), gastric cancer (13), hepatocellular carcinoma (HCC) (14) and lung cancer (15). The downstream targets of miR-433 have been revealed to be strongly associated with cancer development, including Notch1, cAMP responsive element binding protein 1 (CREB1), paired box protein Pax-6 (PAX6), histone deacetylase 6 (HDAC6), kirsten rat sarcoma viral oncogene homolog and hepatocyte growth factor receptor (c-Met) (10,12,13,16 4 and CHANGSHENG YE to be downregulated in these cancer types, and miR-433 was demonstrated to function as a tumor suppressor by inhibiting cell proliferation, migration and differentiation (10,(12)(13)(14)16).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer

Wang

et al. 2018

Oncol Lett

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Abstract. Breast cancer is the most frequently diagnosed malignancy in women. However, the molecular mechanisms underlying breast cancer pathogenesis are not fully understood. The present study examined the role of miR-433 in breast cancer and investigated its underlying molecular mechanisms of action. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to analyze the level of microRNA (miRNA/miR)/mRNA and protein expression, respectively. Additionally, MTT assay was used to determined cell proliferation and viability. Cell apoptosis was measured by flow cytometry. A dual-luciferase reporter assay was used to confirm the identity of the downstream target of miR-433. The results revealed that miR-433 was downregulated in breast cancer tissues and cell lines. Overexpression of miR-433 inhibited cell proliferation and cell viability in BT-549 cells, whereas downregulation of miR-433 increased cell proliferation and cell viability in MDA-MB-231 cells. Further flow cytometry analysis revealed that miR-433 was able to induce apoptosis and also alter the levels of proteins expression of B-cell lymphoma-2 and Bcl-associated X. Bioinformatics analysis showed that RAC-γ serine/threonine-protein kinase (AKT3) was one of the downstream targets of miR-433, and luciferase reporter assay further confirmed that AKT3 is a direct target of miR-433. The knockdown of AKT3 was able to inhibit proliferation and viability in BT-549 cells. Overexpression of AKT3 prevented the inhibitory effects of miR-433 on proliferation and viability in BT-549 cells. The level of AKT3 mRNA expression was upregulated in breast cancer tissues compared with normal tissues and was inversely correlated with miR-433 expression levels. In summary, the results of the present study results indicate that the tumor-suppressive role of miR-433 may be mediated by regulating AKT3. miR-433 may therefore serve as a potential therapeutic target for breast cancer.

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Overexpression of the microRNA miR‐433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells

Cited by 139 publications

References 49 publications

MicroRNA-433 regulates apoptosis by targeting PDCD4 in human osteosarcoma cells

MicroRNA-433 regulates apoptosis by targeting PDCD4 in human osteosarcoma cells

miR‑433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M

MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer

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