Down-regulated long non-coding RNA LHFPL3 antisense RNA 1 inhibits the radiotherapy resistance of nasopharyngeal carcinoma via modulating microRNA-143-5p/homeobox A6 axis

The function of long non-coding RNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) in cancer progression has been studied, while its role in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to unravel the effects of LHFPL3-AS1 on NPC progression via microRNA (miR)-143-5p/homeobox A6 (HOXA6) axis. NPC tissues were collected and NPC cells were cultured. NPC cells were subjected to radiation therapy to construct the radiation therapy resistance NPC cell line. The levels of LHFPL3-AS1, miR-143-5p and HOXA6 in NPC cells and tissues were examined. LHFPL3-AS1, miR-143-5p or HOXA6 expression was changed and then transfected into radiation-resistant NPC cells to detect cell proliferation, colony formation, migration, invasion and cell apoptosis in vitro. The tumorigenesis in nude mice in vivo was conducted to detect tumor growth. The targeting relations among LHFPL3-AS1, miR-143-5p and HOXA6 were validated. It was discovered that LHFPL3-AS1 and HOXA6 expression was elevated while the miR-143-5p level was depleted in radiation-resistant NPC cells and NPC tissues. The silenced LHFPL3-AS1 or augmented miR-143-5p repressed the proliferation, colony formation, migration and invasion of radiation-resistant NPC cells, while accelerated cell apoptosis in vitro. Silenced LHFPL3-AS1 hindered tumor growth in vivo. MiR-143-5p deletion reversed the effects of reduced LHFPL3-AS1; while HOXA6 upregulation reversed the effects of enriched miR-143-5p. LHFPL3-AS1 sponged miR-143-5p that targeted HOXA6. It is concluded that the down-regulated LHFPL3-AS1 retards the development of radiation-resistant NPC cells via sponging miR-143-5p to modulate HOXA6. This study reveals novel therapeutic targets for NPC treatment.

长链非编码RNA LHFPL3反义RNA1（long non-coding RNA LHFPL3 antisense RNA 1, LHFPL3-AS1）在肿瘤进展中的功能已得到广泛研究，但其在鼻咽癌（nasopharyngeal carcinoma, NPC）中的作用仍不明确。本研究旨在通过微小RNA（microRNA, miR）-143-5p/同源框A6（homeobox A6, HOXA6）调控轴，阐明LHFPL3-AS1对鼻咽癌进展的影响。本研究收集鼻咽癌组织并培养鼻咽癌细胞，对鼻咽癌细胞施加放射处理以构建放射抵抗型鼻咽癌细胞系。检测鼻咽癌细胞及组织中LHFPL3-AS1、miR-143-5p及HOXA6的表达水平。通过上调或敲低LHFPL3-AS1、miR-143-5p或HOXA6的表达后转染至放射抵抗型鼻咽癌细胞，体外检测细胞增殖、集落形成、迁移、侵袭及细胞凋亡情况。构建裸鼠体内成瘤模型以检测肿瘤生长情况。验证LHFPL3-AS1、miR-143-5p与HOXA6之间的靶向调控关系。研究发现，在放射抵抗型鼻咽癌细胞及鼻咽癌组织中，LHFPL3-AS1与HOXA6的表达水平升高，而miR-143-5p的表达水平显著下调。敲低LHFPL3-AS1或过表达miR-143-5p可抑制放射抵抗型鼻咽癌细胞的增殖、集落形成、迁移及侵袭能力，同时促进体外细胞凋亡。敲低LHFPL3-AS1可在体内抑制肿瘤生长。miR-143-5p的沉默可逆转LHFPL3-AS1低表达所产生的生物学效应；而HOXA6的过表达可逆转miR-143-5p高表达所产生的生物学效应。LHFPL3-AS1可通过海绵吸附作用结合miR-143-5p，而miR-143-5p可靶向调控HOXA6的表达。综上，低表达LHFPL3-AS1可通过海绵吸附miR-143-5p调控HOXA6的表达，从而延缓放射抵抗型鼻咽癌细胞的进展。本研究为鼻咽癌的治疗揭示了全新的潜在治疗靶点。