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MicroRNA-130b targets PTEN to induce resistance to cisplatin in lung cancer cells by activating Wnt/ß-catenin pathway.
Zhang, Qiang; Zhang, Bin; Sun, Leina; Yan, Qingna; Zhang, Yu; Zhang, Zhenfa; Su, Yanjun; Wang, Changli.
Afiliação
  • Zhang Q; Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
  • Zhang B; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • Sun L; Tianjin Lung Cancer Center, Tianjin, China.
  • Yan Q; Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • Zhang Y; Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
  • Zhang Z; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
  • Su Y; Tianjin Lung Cancer Center, Tianjin, China.
  • Wang C; Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Cell Biochem Funct ; 36(4): 194-202, 2018 Jun.
Article em En | MEDLINE | ID: mdl-29653464
More and more studies indicate the relevance of miRNAs in inducing certain drug resistance. Our study aimed to investigate whether microRNA-130b-3p (miR-130b) mediates the chemoresistance as well as proliferation of lung cancer (LC) cells. MTS assay and apoptosis analysis were conducted to determine cell proliferation and apoptosis, respectively. Binding sites were identified using a luciferase reporter system, whereas mRNA and protein expression of target genes was determined by RT-PCR and immunoblot, respectively. Mouse xenograft model was used to evaluate the role of miR-130b in cisplatin resistance in vivo. The rising level of miR-130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. We identified PTEN as miR-130b's major target and inversely correlated with miR-130b expression in LC. Moreover, excessive miR-130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. Suppression of miR-130b enhanced drug cytotoxicity and reduced proliferation of A549/CR cells both internally and externally. Particularly, miR-130b mediated Wnt/ß-catenin signalling pathway activities, chemoresistance and proliferation in LC cell, which was partially blocked following knockdown of PTEN. These findings suggest that miR-130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/ß-catenin pathway. The rising level of miR-130b in cisplatin resistance LC cell lines (A549/CR and H446/CR) versus its parental cell lines, indicated its crucial relevance for LC biology. Moreover, excessive miR-130b expression promoted drug resistance and proliferation, decreased apoptosis of A549 cells. These findings suggest that miR-130b targets PTEN to mediate chemoresistance, proliferation, and apoptosis via Wnt/ß-catenin pathway.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Resistencia a Medicamentos Antineoplásicos / MicroRNAs / PTEN Fosfo-Hidrolase / Beta Catenina / Via de Sinalização Wnt / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Biochem Funct Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Resistencia a Medicamentos Antineoplásicos / MicroRNAs / PTEN Fosfo-Hidrolase / Beta Catenina / Via de Sinalização Wnt / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Biochem Funct Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China