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长链非编码 RNA LINC01287 通过调控 miR-513a-5p/SERP1 促进宫颈癌的进展。

Long intergenic noncoding RNA LINC01287 drives the progression of cervical cancer via regulating miR-513a-5p/SERP1.

机构信息

Molecular Pharmacology Laboratory, Department of Clinical Pharmacy, Xiangtan Center Hospital, Heping Street 120, Xiangtan, 411100, China.

Department of Pathology and Clinical Laboratories, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.

出版信息

Hum Cell. 2022 Sep;35(5):1577-1590. doi: 10.1007/s13577-022-00755-9. Epub 2022 Jul 27.

Abstract

Cervical cancer is one of the most frequent types of cancer in women, which is characterized by high invasion and metastatic tendency in its advanced stage. Emerging evidence indicated that long non-coding RNAs (LncRNAs) are involved in the pathogenesis of cervical cancer. LINC01287 has been reported to play crucial regulatory roles in the pathogenesis and progression of multiple cancers. However, up until now, whether LINC01287 is associated with the initiation and development of cervical cancer remains largely unknown. In the present study, expression levels of LINC01287, miR-513a-5p and stress-associated endoplasmic reticulum protein 1 (SERP1) mRNA were quantified utilizing qRT-PCR. A series of functional experiments including CCK-8 assay, colony formation assay, transwell assay, flow cytometry, and tumor xenograft growth of cervical cancer cells were performed for studying the effects of LINC01287. The luciferase reporter assay, pull-down assay, and western blot were used to confirm the downstream targets of LINC01287 and miR-513a-5p. The results demonstrate that LINC01287 was highly expressed in cervical cancer tissue samples and cell lines. High LINC01287 predicts a poor prognosis for cervical cancer patients. Additional gain- and loss-of-function experiments demonstrated that silencing LINC01287 inhibited cervical cancer cells proliferation, colony formation, migration, apoptosis in vitro and retarded tumor growth and metastasis in vivo. Furthermore, the dual-luciferase reporter gene system and RNA pulldown assay validated that LINC01287 positively regulated SERP1 expressions by sponging miR-513a-5p, and LINC01287 inhibited cervical cancer progression by regulating miR-513a-5p/SERP1 axis. In conclusion, the current study first identified that LINC01287/miR-513a-5p/SERP1 axis played an important role in cervical cancer progression. LINC01287 might be a prognostic biomarker and a target for new therapies in patients with cervical cancer.

摘要

宫颈癌是女性最常见的癌症类型之一,其在晚期具有高侵袭性和转移倾向。新出现的证据表明,长非编码 RNA(lncRNA)参与了宫颈癌的发病机制。已经有报道称,LINC01287 在多种癌症的发病机制和进展中发挥着关键的调节作用。然而,到目前为止,LINC01287 是否与宫颈癌的发生和发展有关还知之甚少。在本研究中,利用 qRT-PCR 定量检测了 LINC01287、miR-513a-5p 和应激相关内质网蛋白 1(SERP1)mRNA 的表达水平。进行了一系列功能实验,包括 CCK-8 测定、集落形成测定、transwell 测定、流式细胞术和宫颈癌细胞的肿瘤异种移植生长,以研究 LINC01287 的作用。利用荧光素酶报告基因测定、下拉测定和 Western blot 验证了 LINC01287 和 miR-513a-5p 的下游靶标。结果表明,LINC01287 在宫颈癌组织样本和细胞系中高表达。LINC01287 高表达预示着宫颈癌患者预后不良。进一步的增益和缺失功能实验表明,沉默 LINC01287 可抑制宫颈癌细胞的体外增殖、集落形成、迁移和凋亡,并延缓体内肿瘤生长和转移。此外,双荧光素酶报告基因系统和 RNA 下拉实验验证了 LINC01287 通过海绵 miR-513a-5p 正向调节 SERP1 的表达,并且 LINC01287 通过调节 miR-513a-5p/SERP1 轴抑制宫颈癌的进展。总之,本研究首次证实了 LINC01287/miR-513a-5p/SERP1 轴在宫颈癌进展中发挥着重要作用。LINC01287 可能是宫颈癌患者的预后生物标志物和新治疗靶点。

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