长链非编码RNA TEX41通过增加Runx2表达调控肺腺癌骨转移中的自噬。
LncRNA TEX41 regulates autophagy by increasing Runx2 expression in lung adenocarcinoma bone metastasis.
作者信息
Li Rong, Lin Yanping, Hu Fengdi, Liao Yedan, Tang Jiadai, Shen Yan, Li Heng, Guo Jiangyan, Xie Lin
机构信息
Department of Gastrointestinal Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center Kunming, Yunnan, China.
2nd Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center Kunming, Yunnan, China.
出版信息
Am J Transl Res. 2023 Feb 15;15(2):949-966. eCollection 2023.
OBJECTIVE
To investigate the mechanism underlying the role of TEX41 in lung adenocarcinoma (LUAD) bone metastasis (BM).
METHODS
We analyzed the biological functions and molecular mechanisms of TEX41 using bioinformatics. TEX41 and Runx2 expressions were measured in clinical tissue samples and cell lines by quantitative PCR. The effects of TEX41 on LUAD cell proliferation, migration, invasion and metastasis as well as its mechanism of action were investigated. Fluorescence in-situ hybridization (FISH) was performed to determine TEX41 and Runx2 colocalization. Subcutaneous tumor growth and BM were evaluated in nude mice by X-ray and hematoxylin and eosin (HE) staining.
RESULTS
TEX41 was dramatically increased in LUAD BM tissue, indicating a poorer prognosis in patients with LUAD and BM. TEX41 knockdown suppressed the migration and metastasis of LUAD cells, whereas TEX41 overexpression promoted these processes. Data from X-ray and HE staining showed that TEX41 supported the BM in LUAD. TEX41 overexpression induced autophagy in LUAD cells, as demonstrated by changes in autophagy markers. Results of FISH showed that TEX41 and Runx2 colocalized in the nucleus, and Runx2 expression was regulated by TEX41. The effects of TEX41 on LUAD cell migration, invasion, metastasis and autophagy were counteracted by Runx2 inhibition. Moreover, the role of TEX41 in the metastasis was partially dependent on autophagy, and phosphoinositide 3-kinase (PI3K)-AKT might be the major signaling pathway involved in TEX41-regulated autophagy.
CONCLUSION
TEX41 promotes autophagy in LUAD cells by upregulating Runx2 to mediate LUAD migration, invasion and BM.
目的
探讨TEX41在肺腺癌（LUAD）骨转移（BM）中发挥作用的潜在机制。
方法
我们使用生物信息学分析TEX41的生物学功能和分子机制。通过定量PCR检测临床组织样本和细胞系中TEX41和Runx2的表达。研究TEX41对LUAD细胞增殖、迁移、侵袭和转移的影响及其作用机制。进行荧光原位杂交（FISH）以确定TEX41和Runx2的共定位。通过X射线和苏木精-伊红（HE）染色评估裸鼠皮下肿瘤生长和骨转移情况。
结果
TEX41在LUAD骨转移组织中显著增加，这表明LUAD和骨转移患者的预后较差。敲低TEX41可抑制LUAD细胞的迁移和转移，而TEX41过表达则促进这些过程。X射线和HE染色数据显示TEX41促进LUAD的骨转移。TEX41过表达诱导LUAD细胞自噬，这可通过自噬标志物的变化得到证明。FISH结果显示TEX41和Runx2在细胞核中共定位，且Runx2表达受TEX41调控。Runx2抑制可抵消TEX41对LUAD细胞迁移、侵袭、转移和自噬的影响。此外，TEX41在转移中的作用部分依赖于自噬，磷酸肌醇3激酶（PI3K）-AKT可能是参与TEX41调节自噬的主要信号通路。
结论
TEX41通过上调Runx2促进LUAD细胞自噬，从而介导LUAD细胞迁移、侵袭和骨转移。
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