title: Reciprocal regulation of long noncoding RNAs THBS4‑003 and THBS4 control migration and invasion in prostate cancer cell lines.
abstract: Increasing evidence implicates long noncoding RNAs (lncRNAs), a class of noncoding RNAs >200 nucleotides in length, in the development of cancer. However, the mechanism underlying the effects of lncRNAs in prostate cancer (PCa) remains to be elucidated. The present study aimed to investigate the role of lncRNA‑THBS4‑003 in the pathogensis of PCa. In the present study, a microarray containing 8,277 lncRNA probes and 32,207 mRNA probes were used to identify dysregulated mRNAs in three patients with PCa, and reverse transcription‑quantitative polymerase chain reaction was used to determine the expression levels of thrombospondin 4 (THBS4) and lncRNA‑THBS4‑003 in 46 primary PCa and adjacent non‑tumor tissue samples. The expression levels of THBS4 were determined in six samples of PCa and adjacent non‑tumor tissues using Western blot analysis. The effects of forced THBS4 knockdown and lncRNA‑THBS4‑003 knockdown in the two PCa cell lines, DU145 and PC‑3, were evaluated using cell migration and invasion assays, as well as using Western blot analysis. Of the 40,484 probes in the microarray, 354 were significantly upregulated (P<0.05; fold‑change >2). The most significantly upregulated mRNA was THBS4. The expression levels of THBS4 and lncRNA‑THBS4‑003 in the 46 primary PCa samples was significantly higher, compared with that in the adjacent non‑tumor tissue samples. Patients with Gleason scores >7 exhibited higher expression levels of lncRNA‑THBS4‑003, compared with patients with lower scores. Knockdown of THBS4 or lncRNA‑THBS4‑003 significantly reduced the migratory and invasive abilities of the PCa cells in vitro, and decreased the expression levels of p38 and matrix metalloproteinase (MMP)‑9. These findings suggested that the reciprocal regulation of lncRNA‑THBS4‑003 and THBS4 contributed to the pathogenesis of PCa. Therefore silencing lncRNA‑THBS4‑003 or THBS4 may inhibit PCa cell migration and invasion, and regulate the levels of MMP‑9 through the mitogen‑activated protein kinase signaling pathway.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Xiaheng
authors.initials: X
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D019699:Thrombospondins; C101864:thrombospondin 4; D020780:Matrix Metalloproteinase 9