Department of Ultrasonographic, China-Japan Union Hospital of Jilin University, Changchun, China.
Department of Nephrology, Jilin FAW General Hospital, Changchun, China.
Cell Biol Int. 2022 Nov;46(11):1937-1946. doi: 10.1002/cbin.11889. Epub 2022 Aug 30.
Osteosarcoma is prevalent in children and adolescent. The oncogenic function of long-chain noncoding RNA (lncRNA) FGD5 antisense RNA 1 (FGD5-AS1) has been reported. However, the function of FGD5-AS1 in doxorubicin-resistance in osteosarcoma remains to be illucidated. Quantitative real-time PCR (qRT-PCR) and western blot analysis (WB) were used to measure the expression of FGD5-AS1, miR-154-5p, WNT5A and autophagy proteins. MTT assay was used to assess cell viability and transwell assay was performed to evaluate migration. A nude mouse xenograft model was developed to verify the function of FGD5-AS1 in vivo. FGD5-AS1 was upregulated in doxorubicin-resistant (DXR) osteosarcoma cells. Knockdown of FGD5-AS1 suppressed osteosarcoma cell proliferation, migration, and autophagy. FGD5-AS1 upregulated WNT5A expression via sponging miR-154-5p. Furthermore, FGD5-AS1 enhanced osteosarcoma cell chemotherapy resistance through upregulation of WNT5A by inhibiting miR-154-5p. Suppression of FGD5-AS1 significantly suppressed tumor growth in nude mice. FGD5-AS1 may promote chemoresistance through WNT5A-induced autophagy by sponging miR-154-5p in osteosarcoma cells.
成骨肉瘤在儿童和青少年中较为常见。长链非编码 RNA（lncRNA）FGD5 反义 RNA 1（FGD5-AS1）的致癌功能已被报道。然而，FGD5-AS1 在骨肉瘤中对多柔比星耐药的功能仍不清楚。采用实时定量 PCR（qRT-PCR）和 Western blot 分析（WB）检测 FGD5-AS1、miR-154-5p、WNT5A 和自噬蛋白的表达。MTT 法检测细胞活力，Transwell 法评估迁移。建立裸鼠异种移植模型以体内验证 FGD5-AS1 的功能。多柔比星耐药（DXR）骨肉瘤细胞中 FGD5-AS1 上调。FGD5-AS1 敲低抑制骨肉瘤细胞增殖、迁移和自噬。FGD5-AS1 通过海绵吸附 miR-154-5p 上调 WNT5A 表达。此外，FGD5-AS1 通过抑制 miR-154-5p 上调 WNT5A 增强骨肉瘤细胞的化疗耐药性。FGD5-AS1 抑制显著抑制裸鼠肿瘤生长。FGD5-AS1 可能通过海绵吸附 miR-154-5p 促进骨肉瘤细胞中 WNT5A 诱导的自噬来促进化疗耐药性。
