Radiotherapy induced Lewis lung cancer cell apoptosis via inactivating β-catenin mediated by upregulated HOTAIR.

Abstract

OBJECTIVE:

HOTAIR, a long intervening non-coding Hox transcript antisense intergenic RNA, negatively regulates transcription on another chromosome and is reported to reprogram chromatin organization and promote tumor progression. Nevertheless, little is known about its roles in the development of radiation therapy of lung cancer. In this study, we established a xenografed model of Lewis lung carcinoma in C57BL/6 mice and investigated the possible involvement of HOTAIR in this radiotherapy.

METHODS:

C57BL/6 mice were subcutaneously transplanted with Lewis lung carcinoma cells and locally irradiated followed by measurement in tumor volume. Levels of HOTAIR and WIF-1 mRNA expression were determined by using Quantitative Real-Time PCR. Levels of WIF-1 and β-catenin were determined by using western blot assay. Cell viability was evaluated by MTT assay. Cell apoptosis was examined by using TUNEL assay.

RESULTS:

In mice bearing Lewis lung carcinoma tumor, local radiotherapy suppressed tumor growth and it also reduced level of HOTAIR but increased WIF-1 expression. When HOTAIR was overexpressed, radio-sensitivity was reduced. In vitro experiments, irradiation inhibited HOTAIR transportation to the nucleus. However, it was reversed by over-expressed HOTAIR. Cells transfected with pcDNA-HOTAIR or siRNA-HOTAIR resulted in decline or increase in radiosensitivity, which was abrogated by co-tansfected with siRNA-β-catenin.

CONCLUSION:

Radiotherapy induced Lewis lung cancer cell apoptosis via inactivating β-catenin mediated by upregulated HOTAIR.

• Authors: Jianxiang Chen, Zhuping Shen, Yuanda Zheng, Shengye Wang, Weimin Mao
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 7 Pg. 7878-86 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26339352 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• CTNNB1 protein, mouse
• Extracellular Matrix Proteins
• HOTAIR long non-coding RNA, mouse
• Intercellular Signaling Peptides and Proteins
• RNA, Long Noncoding
• RNA, Messenger
• Wif1 protein, mouse
• beta Catenin

Topics

• Adaptor Proteins, Signal Transducing
• Animals
• Apoptosis (radiation effects)
• Carcinoma, Lewis Lung (genetics, metabolism, pathology, radiotherapy)
• Cell Line, Tumor
• Extracellular Matrix Proteins (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Male
• Mice, Inbred C57BL
• RNA Interference
• RNA, Long Noncoding (genetics, metabolism)
• RNA, Messenger (metabolism)
• Signal Transduction (radiation effects)
• Time Factors
• Transfection
• Tumor Burden (radiation effects)
• Up-Regulation
• beta Catenin (genetics, metabolism)