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

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 in vivo. 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.

长链非编码RNA（long non-coding RNAs，lncRNAs）是肿瘤发生发展的关键调控因子，同时具备成为诊断与预后生物标志物的潜在应用价值。FAM83H反义RNA1（FAM83H antisense RNA1，FAM83H-AS1）已被证实为多种癌症的重要调控因子，但目前针对其在肺癌中的作用研究尚少。本研究选用非致瘤性肺细胞系BEAS-2B与肺腺癌细胞系NCI-H1299、HCC827开展实验。此外，本研究通过RNA免疫沉淀（RNA immunoprecipitation）、蛋白质印迹法（Western blotting）、定量逆转录聚合酶链反应（quantitative reverse transcription-PCR，qRT-PCR）以及荧光素酶报告基因实验（luciferase reporter assays），解析FAM83H-AS1在肺癌进展中的调控作用。实验结果表明，FAM83H-AS1在肺癌组织中呈高表达；敲低该基因可抑制肺癌细胞的侵袭与增殖能力，并在体内延缓肿瘤生长。此外，本研究发现FAM83H-AS1可靶向结合miR-545-3p，二者在肺癌组织中的表达水平呈负相关。同时，miR-545-3p可负调控硫酸乙酰肝素6-O-磺基转移酶（heparan sulfate 6-O-sulfotransferase，HS6ST2）。进一步实验发现，抑制miR-545-3p的表达可上调HS6ST2蛋白水平并促进肺癌细胞侵袭。综上，FAM83H-AS1通过靶向调控miR-545-3p/HS6ST2轴促进非小细胞肺癌的进展，这一发现为将FAM83H-AS1开发为非小细胞肺癌的干预靶点提供了理论依据。