Qinhua Liu1, Ruonan Ran2, Mingyue Song3, Xiaodan Li1, Zhengsheng Wu4, Guanrong Dai1, Ruixiang Xia5. 1. Department of Hematology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, 230022, Anhui, China. 2. Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University, Hefei, China. 3. Department of Hematology, the Chaohu Hospital Affiliated to Anhui Medical University, Chaohu, Anhui, China. 4. Department of Pathology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. 5. Department of Hematology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, 230022, Anhui, China. RuixiangXiaHospita@163.com.
Abstract
BACKGROUND: Although long non-coding RNA (lncRNA) HCP plays essential roles in human cancers, its function and mechanism in multiple myeloma (MM) have not crystallized. METHODS: HCP5 level in MM was assessed through qRT-PCR. A series of functional investigations were conducted to evaluate the influences of HCP5 on proliferation and apoptosis. Bioinformatics analysis and RIP/RNA pull-down assays were carried out to determine the relationships among HCP5, miR-128-3p, and PLAGL2. Relative protein level was determined through Western blot. A xenograft tumor model was applied for validating the roles of HCP5/miR-128-3p/PLAGL2 axis in vivo. RESULTS: HCP5 was significantly increased in MM. HCP5 knockdown effectively thwarted the proliferative rate and cell cycle of MM cell lines and suppressed tumor growth. HCP5 regulated PLAGL2 expression by sponging miR-128-3p. PLAGL2 overexpression effectively rescued cells from influences by sh-HCP5 on cell proliferative and apoptotic rates. Additionally, HCP5 knockdown significantly inhibited Wnt/β-catenin/cyclin D1 signaling, and these effects were eliminated by PLAGL2 overexpression. CONCLUSION: Our study revealed that HCP5/miR-128-3p/PLAGL2 is closely correlated to MM development by modulating Wnt/β-catenin/cyclin D1 signaling. HCP5 promoted cell proliferation and tumor formation of MM cells by activating the Wnt/β-catenin/CCND1 signaling pathway by sponging miR-128-3p to increase PLAGL2 expression.
BACKGROUND: Although long non-coding RNA (lncRNA) HCP plays essential roles in humancancers, its function and mechanism in multiple myeloma (MM) have not crystallized. METHODS:HCP5 level in MM was assessed through qRT-PCR. A series of functional investigations were conducted to evaluate the influences of HCP5 on proliferation and apoptosis. Bioinformatics analysis and RIP/RNA pull-down assays were carried out to determine the relationships among HCP5, miR-128-3p, and PLAGL2. Relative protein level was determined through Western blot. A xenograft tumor model was applied for validating the roles of HCP5/miR-128-3p/PLAGL2 axis in vivo. RESULTS:HCP5 was significantly increased in MM. HCP5 knockdown effectively thwarted the proliferative rate and cell cycle of MM cell lines and suppressed tumor growth. HCP5 regulated PLAGL2 expression by sponging miR-128-3p. PLAGL2 overexpression effectively rescued cells from influences by sh-HCP5 on cell proliferative and apoptotic rates. Additionally, HCP5 knockdown significantly inhibited Wnt/β-catenin/cyclin D1 signaling, and these effects were eliminated by PLAGL2 overexpression. CONCLUSION: Our study revealed that HCP5/miR-128-3p/PLAGL2 is closely correlated to MM development by modulating Wnt/β-catenin/cyclin D1 signaling. HCP5 promoted cell proliferation and tumor formation of MM cells by activating the Wnt/β-catenin/CCND1 signaling pathway by sponging miR-128-3p to increase PLAGL2 expression.
Authors: Kate Baker; Sarah L Gordon; Holly Melland; Fabian Bumbak; Daniel J Scott; Tess J Jiang; David Owen; Bradley J Turner; Stewart G Boyd; Mari Rossi; Mohammed Al-Raqad; Orly Elpeleg; Dawn Peck; Grazia M S Mancini; Martina Wilke; Marcella Zollino; Giuseppe Marangi; Heike Weigand; Ingo Borggraefe; Tobias Haack; Zornitza Stark; Simon Sadedin; Tiong Yang Tan; Yunyun Jiang; Richard A Gibbs; Sara Ellingwood; Michelle Amaral; Whitley Kelley; Manju A Kurian; Michael A Cousin; F Lucy Raymond Journal: Brain Date: 2018-09-01 Impact factor: 13.501