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lncRNA PSMB8-AS1 通过海绵吸附 miR-1299 来上调 ADAMTS5 促进结直肠癌进展。

lncRNA PSMB8-AS1 promotes colorectal cancer progression through sponging miR-1299 to upregulate ADAMTS5.

机构信息

Department of Oncology, The Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shanxi, China.

出版信息

Neoplasma. 2022 Sep;69(5):1138-1153. doi: 10.4149/neo_2022_220111N42. Epub 2022 Jun 30.

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be vital participants in tumor progression. Recently, lncRNA PSMB8-AS1 has been uncovered to facilitate pancreatic cancer progression by regulating miR-382-3p/STAT1/PD-L1 network. Nonetheless, the role of PSMB8-AS1 and its underlying mechanism have not been well-explored in colorectal cancer (CRC). The expression of RNAs or proteins was detected via qRT-PCR or western blot assays. Functional assays were involved in evaluating the effects of PSMB8-AS1/miR-1299/ADAMTS5 on the malignant behaviors of CRC cells. The molecular mechanism of PSMB8-AS1 was explored via mechanism analyses in CRC cells. Based on experimental results, PSMB8-AS1 expression was notably higher in CRC cell lines than in normal cells. The downregulation of PSMB8-AS1 repressed cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC while promoting cell apoptosis. It was also revealed that PSMB8-AS1 could sponge miR-1299 to upregulate ADAMTS5 in CRC cells. In rescue assays, we further discovered that miR-1299 inhibition or ADAMTS5 overexpression abrogated the suppressive influence of PSMB8-AS1 deficiency on CRC cell growth. In addition, PSMB8-AS1 was validated to induce M2 polarization. In conclusion, PSMB8-AS1 sponges miR-1299 to increase PSMB8-AS1 expression, thus promoting CRC cell growth.

摘要

长链非编码 RNA(lncRNA)已被报道是肿瘤进展的重要参与者。最近,lncRNA PSMB8-AS1 被发现通过调节 miR-382-3p/STAT1/PD-L1 网络促进胰腺癌的进展。然而,PSMB8-AS1 的作用及其潜在机制在结直肠癌(CRC)中尚未得到充分探索。通过 qRT-PCR 或 Western blot 检测 RNA 或蛋白质的表达。通过评估 PSMB8-AS1/miR-1299/ADAMTS5 对 CRC 细胞恶性行为的影响进行功能分析。通过 CRC 细胞的机制分析探索 PSMB8-AS1 的分子机制。基于实验结果,PSMB8-AS1 在 CRC 细胞系中的表达明显高于正常细胞。下调 PSMB8-AS1 抑制 CRC 细胞的活力、增殖、迁移、侵袭和上皮-间充质转化(EMT),同时促进细胞凋亡。还发现 PSMB8-AS1 可以海绵 miR-1299 以上调 CRC 细胞中的 ADAMTS5。在挽救实验中,我们进一步发现 miR-1299 抑制或 ADAMTS5 过表达消除了 PSMB8-AS1 缺乏对 CRC 细胞生长的抑制作用。此外,PSMB8-AS1 被证实诱导 M2 极化。总之,PSMB8-AS1 海绵 miR-1299 增加 PSMB8-AS1 的表达,从而促进 CRC 细胞的生长。

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