Wang Faming, Luo Yao, Zhang Le, Younis Muhammad, Yuan Liudi
Department of Biochemistry and Molecular Biology, Medical School of Southeast University, Nanjing, China.
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
Cancer Gene Ther. 2022 Mar;29(3-4):292-303. doi: 10.1038/s41417-021-00309-5. Epub 2021 Mar 11.
Long non-coding RNAs (lncRNAs) have recently been reported to act as crucial regulators and prognostic biomarkers of human tumorigenesis. Based on microarray data, RP11-301G19.1 was previously identified as an upregulated lncRNA during B cell development. However, the effect of RP11-301G19.1 on multiple myeloma (MM) cells remains unclear. In the present study, the effects of RP11-301G19.1 on tumour progression were ascertained both in vitro and in vivo. Our results demonstrated that RP11-301G19.1 was upregulated in MM cell lines and that its downregulation inhibited the proliferation and cell cycle progression and promoted the apoptosis of MM cells. Bioinformatic analysis and luciferase reporter assay results revealed that RP11-301G19.1 can upregulate the miR-582-5p-targeted gene HMGB2 as a competing endogenous RNA (ceRNA). Furthermore, Western blot results indicated that RP11-301G19.1 knockdown decreased the levels of PI3K and AKT phosphorylation without affecting their total protein levels. Additionally, in a xenograft model of human MM, RP11-301G19.1 knockdown significantly inhibited tumour growth by downregulating HMGB2. Overall, our data demonstrated that RP11-301G19.1 is involved in MM cell proliferation by sponging miR-582-5p and may serve as a therapeutic target for MM.
最近有报道称，长链非编码RNA（lncRNAs）在人类肿瘤发生过程中起着关键调节作用和预后生物标志物的作用。基于微阵列数据，RP11-301G19.1先前被鉴定为B细胞发育过程中上调的lncRNA。然而，RP11-301G19.1对多发性骨髓瘤（MM）细胞的影响仍不清楚。在本研究中，我们在体外和体内确定了RP11-301G19.1对肿瘤进展的影响。我们的结果表明，RP11-301G19.1在MM细胞系中上调，其下调抑制了MM细胞的增殖和细胞周期进程，并促进了MM细胞的凋亡。生物信息学分析和荧光素酶报告基因检测结果显示，RP11-301G19.1可以作为竞争性内源RNA（ceRNA）上调miR-582-5p靶向基因HMGB2。此外，蛋白质印迹结果表明，敲低RP11-301G19.1可降低PI3K和AKT的磷酸化水平，但不影响其总蛋白水平。此外，在人MM异种移植模型中，敲低RP11-301G19.1可通过下调HMGB2显著抑制肿瘤生长。总体而言，我们的数据表明，RP11-301G19.1通过海绵吸附miR-582-5p参与MM细胞增殖，可能作为MM的治疗靶点。
