Xing Biao, Qiao Xiao-Feng, Qiu Yan-Hua, Li Xin
Department of Otolaryngology, Cangzhou Central Hospital, Cangzhou, Hebei, People's Republic of China.
Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, People's Republic of China.
Cancer Manag Res. 2021 Jan 15;13:415-425. doi: 10.2147/CMAR.S285113. eCollection 2021.
Previous evidence demonstrates that the long non-coding RNA (lncRNA) TMPO antisense RNA 1 (TMPO-AS1) is involved in the aggressiveness of several cancers. Nevertheless, its functions in nasopharyngeal carcinoma (NPC) are unclear.
qRT-PCR was used to evaluate the levels of TMPO-AS1 and miR-320a in NPC tissues. Furthermore, the growth and invasiveness of NPC cells were evaluated by colony formation and Transwell assays. The protein expression ofSRY-Box Transcription Factor 4 (SOX4) was observed by Western blotting and immunohistochemistry. Bioinformatic prediction and luciferase reporter assays were used to explore the interaction between miR-320a and TMPO-AS1. The transplanted model was employed to disclose the interference of TMPO-AS1 in the tumor growth of NPC cells in vivo.
We found that TMPO-AS1 was distinctly upregulated in NPC. Downregulation of TMPO-AS1 restrained aggressiveness-associated traits in NPC cells. Nevertheless, upregulation of TMPO-AS1 yielded the opposite results. Further studies revealed that lncRNA TMPO-AS1 acts as a "sponge" for miR-320a, resulting in increased levels of SOX4 in NPC cells. Finally, TMPO-AS1 silencing suppressed tumor growth of NPC cells in vivo.
Collectively, these results reveal the presence of a novel TMPO-AS1/miR-320a/SOX4 pathway associated with NPC progression, suggesting that lncRNA TMPO-AS1 may be a potential therapeutic target for NPC.
先前的证据表明，长链非编码RNA（lncRNA）TMPO反义RNA 1（TMPO-AS1）参与了多种癌症的侵袭性。然而，其在鼻咽癌（NPC）中的功能尚不清楚。
采用qRT-PCR评估NPC组织中TMPO-AS1和miR-320a的水平。此外，通过集落形成和Transwell实验评估NPC细胞的生长和侵袭能力。通过蛋白质印迹法和免疫组织化学观察SRY盒转录因子4（SOX4）的蛋白表达。利用生物信息学预测和荧光素酶报告基因实验探索miR-320a与TMPO-AS1之间的相互作用。采用移植模型揭示TMPO-AS1对NPC细胞体内肿瘤生长的干扰作用。
我们发现TMPO-AS1在NPC中明显上调。TMPO-AS1的下调抑制了NPC细胞中与侵袭性相关的特征。然而，TMPO-AS1的上调产生了相反的结果。进一步研究表明，lncRNA TMPO-AS1作为miR-320a的“海绵”，导致NPC细胞中SOX4水平升高。最后，TMPO-AS1沉默抑制了NPC细胞在体内的肿瘤生长。
总体而言，这些结果揭示了一条与NPC进展相关的新型TMPO-AS1/miR-320a/SOX4通路，表明lncRNA TMPO-AS1可能是NPC的一个潜在治疗靶点。
