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长链非编码 RNA FAM83H 反义 RNA1(FAM83H-AS1)通过调节 miR-545-3p/硫酸乙酰肝素 6-O-磺基转移酶 2(HS6ST2)轴在非小细胞肺癌进展中的作用。

Role of lncRNA FAM83H antisense RNA1 (FAM83H-AS1) in the progression of non-small cell lung cancer by regulating the miR-545-3p/heparan sulfate 6-O-sulfotransferase (HS6ST2) axis.

机构信息

Department of Thoracic Oncology, Lung Cancer Diagnosis and Treatment Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Department of Mammography Surgery, The First Affiliated Hospital of HeBei North University, Zhangjiakou, Hebei, China.

出版信息

Bioengineered. 2022 Mar;13(3):6476-6489. doi: 10.1080/21655979.2022.2031668.

Abstract

Long non-coding RNAs (lncRNAs) are crucial regulators of cancer pathogenesis and are potentially useful diagnostic and prognostic biomarker tools. FAM83H antisense RNA1 (FAM83H-AS1) has been reported to be a vital regulator of different cancers; however, little attention has been paid to its significance in lung cancer. Non-tumorigenic lung cell line BEAS-2B and adenocarcinoma lung cancer cell lines NCI-H1299 and HCC827 were used in the present study. In addition, RNA immunoprecipitation, Western blotting, quantitative reverse transcription-PCR (qRT-PCR), and luciferase reporter assays were used to dissect the role of FAM83H-AS1 in lung cancer progression. The results revealed that FAM83H-AS1 is highly expressed in lung cancer tissues, and its knockdown inhibits lung cancer cell invasion and proliferation reducing tumor growth . Besides, we found that FAM83H-AS1 targets miR-545-3p, and a negative correlation exists between their expression in lung cancer tissues. Simultaneously, miR-545-3p negatively regulates heparan sulfate 6-O-sulfotransferase (HS6ST2). Moreover, inhibition of miR-545-3p promoted HS6ST2 protein expression and lung cancer cell invasion. FAM83H-AS1 favors non-small cell lung cancer by targeting the miR-545-3p/HS6ST2 axis, supporting the possibility of developing FAM83H-AS1 as a target for NSCLC intervention.

摘要

长链非编码 RNA(lncRNA)是癌症发病机制的重要调节因子,是潜在的有用的诊断和预后生物标志物工具。已经有报道称 FAM83H 反义 RNA1(FAM83H-AS1)是不同癌症的重要调节因子;然而,人们对其在肺癌中的意义关注甚少。本研究使用非致瘤性肺细胞系 BEAS-2B 和腺癌肺癌细胞系 NCI-H1299 和 HCC827。此外,还使用 RNA 免疫沉淀、Western blot、定量逆转录-PCR(qRT-PCR)和荧光素酶报告基因测定来剖析 FAM83H-AS1 在肺癌进展中的作用。结果表明,FAM83H-AS1 在肺癌组织中高表达,其敲低抑制肺癌细胞侵袭和增殖,从而抑制肿瘤生长。此外,我们发现 FAM83H-AS1 靶向 miR-545-3p,并且它们在肺癌组织中的表达存在负相关。同时,miR-545-3p 负调控硫酸乙酰肝素 6-O-磺基转移酶(HS6ST2)。此外,抑制 miR-545-3p 促进了 HS6ST2 蛋白表达和肺癌细胞侵袭。FAM83H-AS1 通过靶向 miR-545-3p/HS6ST2 轴促进非小细胞肺癌,支持将 FAM83H-AS1 作为 NSCLC 干预靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36b4/8973780/efa8df50fe68/KBIE_A_2031668_UF0001_OC.jpg

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