LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating <i>ITGAV</i> transcription

Kang, Chun Lan; Qi, Bing; Cai, Qian Qian; Fu, Li Sheng; Yang, Ying; Tang, Chang; Zhu, Ping; Chen, Qi Wen; Pan, Jing; Chen, Mei Hua; Wu, Xing Zhong

doi:10.7150/thno.32854

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Nanotheranostics 2024; 8(4): 442-457. [Abstract] [Full text] [PDF]

Nanotheranostics 2024; 8(4): 427-441. [Abstract] [Full text] [PDF]

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Theranostics 2019; 9(15):4421-4436. doi:10.7150/thno.32854 This issue Cite

Research Paper

LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription

Chun Lan Kang^1*, Bing Qi^1*, Qian Qian Cai¹, Li Sheng Fu¹, Ying Yang¹, Chang Tang¹, Ping Zhu², Qi Wen Chen³, Jing Pan⁴, Mei Hua Chen¹, Xing Zhong Wu^1✉

1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, NHC Key Laboratory of Glycoconjugates Research (Fudan University), Shanghai, P.R. China.
2. Zhejiang Provincial People's Hospital, Hangzhou, P,R. China.
3. Tumor Hospital, Fudan University, P,R. China.
4. The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, P. R. China.
* These authors contributed equally to this study.

Citation:

Kang CL, Qi B, Cai QQ, Fu LS, Yang Y, Tang C, Zhu P, Chen QW, Pan J, Chen MH, Wu XZ. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics 2019; 9(15):4421-4436. doi:10.7150/thno.32854. https://www.thno.org/v09p4421.htm

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Abstract

Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis.

Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in sulfatide-treated cells. Mass spectrometry, protein arrays, and RNA pull-down experiments were used to identify proteins that interacted with lncRNA. Epigenetic analysis was used to study lncRNA-mediated regulation mechanisms.

Results: We identified lncRNA AY927503 (AY) as a metastasis-associated molecule that was highly expressed in human hepatocellular carcinoma (HCC) and correlated with metastatic events and poor prognosis in patients with HCC. AY promoted HCC cell migration, stemness, 5-fluorouracil resistance, and metastasis in mice. However, knockdown of integrin αV (ITGAV) abolished AY-stimulated migration, cell viability in HCC cells or tube formation. AY strongly promoted ITGAV transcription and αVβ3 expression by interacting with the ITGAV promoter specifically and stimulating its activity. AY was identified to interact with histone 1FX (H1FX), but deletion of the central domain of AY (AY∆371-522) abolished H1FX binding and ITGAV promoter stimulation. AY significantly enriched H3K4Me3 and acH3K9/14 but reduced H3K27Me3 and H1FX occupancy on the ITGAV promoter, which remodeled chromatin structures for RNA polymerase II recruitment. Knockdown of H1FX abrogated ITGAV transcription stimulated by AY.

Conclusions: Our findings suggested that lncRNA AY promoted HCC metastasis via induction of chromatin modification for ITGAV transcription as a pioneer factor and was a potential molecular signature for metastasis or poor prognosis in patients with HCC.

Keywords: metastasis, integrin, migration, linker histone, epigenetics

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APA

Kang, C.L., Qi, B., Cai, Q.Q., Fu, L.S., Yang, Y., Tang, C., Zhu, P., Chen, Q.W., Pan, J., Chen, M.H., Wu, X.Z. (2019). LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics, 9(15), 4421-4436. https://doi.org/10.7150/thno.32854.

ACS

Kang, C.L.; Qi, B.; Cai, Q.Q.; Fu, L.S.; Yang, Y.; Tang, C.; Zhu, P.; Chen, Q.W.; Pan, J.; Chen, M.H.; Wu, X.Z. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics 2019, 9 (15), 4421-4436. DOI: 10.7150/thno.32854.

NLM

CSE

Kang CL, Qi B, Cai QQ, Fu LS, Yang Y, Tang C, Zhu P, Chen QW, Pan J, Chen MH, Wu XZ. 2019. LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription. Theranostics. 9(15):4421-4436.

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