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长链非编码 RNA HOTAIR 通过促进 HIF-1α 的表达导致人宫颈癌的放射抵抗。

Overexpression of HOTAIR leads to radioresistance of human cervical cancer via promoting HIF-1α expression.

机构信息

Tumor Diagnosis and Treatment Center of Kaifeng Central Hospital, No 85 HeDao street, Longting District, Kaifeng, 475001, Henan, China.

出版信息

Radiat Oncol. 2018 Oct 24;13(1):210. doi: 10.1186/s13014-018-1153-4.

DOI:10.1186/s13014-018-1153-4
PMID:30355300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6201557/
Abstract

BACKGROUND

HOTAIR was known to enhance radioresistance in several cancers. However, the function of HOTAIR on radioresistance involving the regulation of HIF-1α in cervical cancer has not been reported.

METHODS

BALB/c nude mice were injected subcutaneously with HeLa cells and irradiated by X-ray. The tumor volume was measured and the expression of HOTAIR in tumors was detected by quantitative real-time PCR. Western blot was performed to detect the protein level of HIF-1α. MTT (3-(4,5-Dimethylthiazol-2-yl) 22,5-diphenyltetrazolium bromide) assay and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to examine the cell viability and cell apoptosis of HeLa cells and C33A cells exposed to radiation.

RESULTS

Radiotherapy inhibited the tumor growth in mice bearing HeLa cells. Radiotherapy reduced the expression of HOTAIR and HIF-1α in tumor tissues and HeLa cells or C33A cells. HOTAIR overexpression abrogated the effect of radiation on the cell viability and cell apoptosis of HeLa and C33A cells. HOTAIR also upregulated the expression of HIF-1α in HeLa and C33A cell exposed to radiation. HIF-1α knockdown reversed increasing cell viability and reducing apoptosis of HeLa and C33A cell induced by HOTAIR overexpression. HOTAIR overexpression promoted tumor growth in mice bearing HeLa and exposed to radiation.

CONCLUSION

Radiotherapy might inhibit cervical cancer cell growth through HOTAIR/HIF-1α pathway.

摘要

背景

已知 HOTAIR 可增强几种癌症的放射抗性。然而,HOTAIR 对涉及宫颈癌中 HIF-1α 调节的放射抗性的功能尚未报道。

方法

BALB/c 裸鼠皮下注射 HeLa 细胞并用 X 射线照射。测量肿瘤体积,并通过定量实时 PCR 检测肿瘤中 HOTAIR 的表达。通过 Western blot 检测 HIF-1α 的蛋白水平。MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐)测定和末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)测定用于检测暴露于辐射的 HeLa 细胞和 C33A 细胞的细胞活力和细胞凋亡。

结果

放射治疗抑制了携带 HeLa 细胞的小鼠的肿瘤生长。放射治疗降低了肿瘤组织以及 HeLa 细胞或 C33A 细胞中 HOTAIR 和 HIF-1α 的表达。HOTAIR 过表达消除了辐射对 HeLa 和 C33A 细胞活力和细胞凋亡的影响。HOTAIR 还上调了暴露于辐射的 HeLa 和 C33A 细胞中 HIF-1α 的表达。HIF-1α 敲低逆转了 HOTAIR 过表达诱导的 HeLa 和 C33A 细胞活力增加和凋亡减少。HOTAIR 过表达促进了携带 HeLa 并暴露于辐射的小鼠的肿瘤生长。

结论

放射治疗可能通过 HOTAIR/HIF-1α 通路抑制宫颈癌细胞生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/e7248c94298a/13014_2018_1153_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/dfc9bd43ff01/13014_2018_1153_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/99d2a650c424/13014_2018_1153_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/65239141a00f/13014_2018_1153_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/8cb2de81f2b9/13014_2018_1153_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/31408bfdaf19/13014_2018_1153_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/e7248c94298a/13014_2018_1153_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/dfc9bd43ff01/13014_2018_1153_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/99d2a650c424/13014_2018_1153_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/65239141a00f/13014_2018_1153_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/8cb2de81f2b9/13014_2018_1153_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/31408bfdaf19/13014_2018_1153_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d7a/6201557/e7248c94298a/13014_2018_1153_Fig6_HTML.jpg

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