LncRNA HCP5 acts as a miR-128-3p sponge to promote the progression of multiple myeloma through activating Wnt/β‐catenin/cyclin D1 signaling via PLAGL2,Cell Biology and Toxicology

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LncRNA HCP5 acts as a miR-128-3p sponge to promote the progression of multiple myeloma through activating Wnt/β‐catenin/cyclin D1 signaling via PLAGL2
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-07-31 , DOI: 10.1007/s10565-021-09628-7
Qinhua Liu ₁ , Ruonan Ran ₂ , Mingyue Song ₃ , Xiaodan Li ₁ , Zhengsheng Wu ₄ , Guanrong Dai ₁ , Ruixiang Xia ₁

Affiliation

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.

Graphical abstract

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

中文翻译：

LncRNA HCP5 作为 miR-128-3p 海绵通过 PLAGL2 激活 Wnt/β-catenin/cyclin D1 信号通路促进多发性骨髓瘤的进展

背景

尽管长链非编码 RNA (lncRNA) HCP 在人类癌症中起着重要作用，但其在多发性骨髓瘤 (MM) 中的功能和机制尚未明确。

方法

通过 qRT-PCR 评估 MM 中的 HCP5 水平。进行了一系列功能研究以评估 HCP5 对增殖和凋亡的影响。进行生物信息学分析和 RIP/RNA pull-down 测定以确定 HCP5、miR-128-3p 和 PLAGL2 之间的关系。通过蛋白质印迹确定相对蛋白质水平。异种移植肿瘤模型用于验证 HCP5/miR-128-3p/PLAGL2 轴在体内的作用。

结果

HCP5 在 MM 中显着增加。HCP5 敲低有效地阻碍了 MM 细胞系的增殖率和细胞周期，并抑制了肿瘤生长。HCP5 通过海绵化 miR-128-3p 调节 PLAGL2 表达。PLAGL2 过表达有效地使细胞免受 sh-HCP5 对细胞增殖和凋亡率的影响。此外，HCP5 敲低显着抑制了 Wnt/β-连环蛋白/细胞周期蛋白 D1 信号传导，并且 PLAGL2 过表达消除了这些影响。