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长链非编码 RNA HOXB-AS3 通过激活 PI3K-AKT 通路促进肺癌的增殖、迁移和侵袭。

lncRNA HOXB-AS3 exacerbates proliferation, migration, and invasion of lung cancer via activating the PI3K-AKT pathway.

机构信息

Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Thoracic Surgery, Hubei Cancer Hospital, Wuhan, China.

出版信息

J Cell Physiol. 2020 Oct;235(10):7194-7203. doi: 10.1002/jcp.29618. Epub 2020 Feb 10.

DOI:10.1002/jcp.29618
PMID:32039488
Abstract

Lung cancer remains the leading cause of cancer-related death all over the world. In spite of the great advances made in surgery and chemotherapy, the prognosis of lung cancer patients is poor. A substantial fraction of long noncoding RNAs (lncRNAs) can regulate various cancers. A recent study has reported that lncRNA HOXB-AS3 plays a critical role in cancers. However, its biological function remains unclear in lung cancer progression. In the current research, we found HOXB-AS3 was obviously elevated in NSCLC tissues and cells. Functional assays showed that inhibition of HOXB-AS3 was able to repress A549 and H1975 cell proliferation, cell colony formation ability and meanwhile, triggered cell apoptosis. Furthermore, the lung cancer cell cycle was mostly blocked in the G1 phase whereas the cell ratio in the S phase was reduced. Also, A549 and H1975 cell migration and invasion capacity were significantly repressed by the loss of HOXB-AS3. The PI3K/AKT pathway has been implicated in the carcinogenesis of multiple cancers. Here, we displayed that inhibition of HOXB-AS3 suppressed lung cancer cell progression via inactivating the PI3K/AKT pathway. Subsequently, in vivo experiments were utilized in our study and it was demonstrated that HOXB-AS3 contributed to lung cancer tumor growth via modulating the PI3K/AKT pathway. Overall, we implied that HOXB-AS3 might provide a new perspective for lung cancer treatment via targeting PI3K/AKT.

摘要

肺癌仍然是全球癌症相关死亡的主要原因。尽管在手术和化疗方面取得了巨大进展,但肺癌患者的预后仍然不佳。大量长链非编码 RNA(lncRNA)可以调节各种癌症。最近的一项研究报告称,lncRNA HOXB-AS3 在癌症中发挥着关键作用。然而,其在肺癌进展中的生物学功能尚不清楚。在当前的研究中,我们发现 HOXB-AS3 在 NSCLC 组织和细胞中明显升高。功能测定表明,抑制 HOXB-AS3 能够抑制 A549 和 H1975 细胞的增殖、细胞集落形成能力,同时触发细胞凋亡。此外,肺癌细胞周期主要被阻滞在 G1 期,而 S 期的细胞比例减少。此外,HOXB-AS3 的缺失明显抑制了 A549 和 H1975 细胞的迁移和侵袭能力。PI3K/AKT 通路参与了多种癌症的发生。在这里,我们显示抑制 HOXB-AS3 通过失活 PI3K/AKT 通路抑制肺癌细胞的进展。随后,在我们的研究中进行了体内实验,证明 HOXB-AS3 通过调节 PI3K/AKT 通路促进肺癌肿瘤的生长。总的来说,我们暗示 HOXB-AS3 可能通过靶向 PI3K/AKT 为肺癌治疗提供新的视角。

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