title: MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression.
abstract: Paclitaxel (Taxol) is an effective chemotherapeutic agent for treating breast cancer patients. However, chemoresistance is a major obstacle in cancer treatment. Here, we showed that overexpression of miR-16 promoted Taxol-induced cytotoxicity and apoptosis in breast cancer cells. Furthermore, IκB kinase β (IKBKB) was identified as a direct target of miR-16. Up-regulation of IKBKB suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol, and restoring IKBKB expression in miR-16-overexpressing breast cancer cells recovered Taxol resistance. Moreover, miR-16 was highly expressed in Taxol-sensitive breast cancer tissues compared with Taxol-resistant tissues, and there was an inverse correlation between miR-16 expression and IKBKB expression in breast cancer tissues. The expression levels of miR-16 were negatively associated with T stages, whereas the expression of IKBKB was positively correlated with T stages, lymph node metastasis and clinical stages. Taken together, our data demonstrates that miR-16 sensitizes breast cancer cells to Taxol through the suppression of IKBKB expression, and targeting miR-16/IKBKB axis will be a promising strategy for overcoming Taxol resistance in breast cancer.
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Peiguo
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Cao
authors.affiliation: Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Chenghui
authors.initials: C
authors.lastname: Huang
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Shourong
authors.initials: S
authors.lastname: Shen
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Xiayu
authors.initials: X
authors.lastname: Li
authors.affiliation: The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; D017239:Paclitaxel
keywords: IKBKB; Taxol; breast cancer; chemosensitivity; miR-16