Premium
Knockdown of the long noncoding RNA HOTTIP inhibits cell proliferation and enhances cell sensitivity to cisplatin by suppressing the Wnt/β‐catenin pathway in prostate cancer
Author(s) -
Jiang Huichuan,
Xiong Wei,
Chen Lingxiao,
Lv Zhengtong,
Yang Changzhao,
Li Yuan
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27851
Subject(s) - cell cycle , wnt signaling pathway , gene knockdown , cell growth , cancer research , cisplatin , biology , long non coding rna , flow cytometry , cell , catenin , mtt assay , microbiology and biotechnology , cell culture , signal transduction , downregulation and upregulation , gene , genetics , chemotherapy
Abstract Background Prostate cancer (PCa) is a prevalent and deadly cancer worldwide. Considering the malignant progression and therapeutic resistance of PCa, further dissection of the underlying mechanisms and exploration of novel therapeutic targets for PCa are urgently needed. The long noncoding RNA HOTTIP has recently been revealed as an oncogenic regulator in different cancers; however, whether HOTTIP is involved in PCa remains poorly understood. Here, we examined the crucial roles of HOTTIP in the proliferation and chemoresistance of PCa. Methods Quantitative real‐time PCR (qRT‐PCR) was performed to detect the HOTTIP messenger RNA (mRNA) levels in PCa samples from patients and PCa cells. Then, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), colony formation, and cell cycle and flow cytometry assays were performed to investigate the proliferation and cisplatin‐resistance of PCa cells with silenced HOTTIP compared with a negative control. We applied Western blotting, qRT‐PCR and a TOP/FOP assay to explore the relevant mechanisms. Results In this study, we found that the HOTTIP mRNA levels were increased in the PCa patient samples and PCa cell lines compared with the controls. The knockdown of HOTTIP not only inhibited the proliferation of PCa cells but also facilitated cell cycle arrest and chemosensitivity to cisplatin. Furthermore, the qRT‐PCR, Western blotting, TOP/FOP assays, MTT assay, and flow cytometry revealed that Wnt/β‐catenin signaling was related to the regulation of HOTTIP in cell proliferation, cell cycle arrest, and chemoresistance to cisplatin in PCa. Conclusion Taken together, our findings suggest that HOTTIP may be a potent therapeutic target for PCa, and HOTTIP inhibitors might be regarded as effective strategies for PCa therapy.