HPV18 E6 and E7 Influence the Expression of Cancer Related LncRNAs in HeLa Cells
Cervical cancer which is identified as the second most common type of cancer in women worldwide, is responsible for more than 275,100 mortalities each year and associated with the long-term infection of high-risk human papillomavirus, including HPV18. HPV
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1 Introduction Cervical cancer which is identified as the second most common type of cancer in women worldwide, is responsible for more than 275,100 mortalities each year and associated with high-risk human papillomavirus, including HPV18 [1]. HPV18 DNA contains two vital oncogenes, E6 and E7, which have crucial roles in malignant transformation in cervical cancer. The E6 promotes p53 degradation through E6AP interaction [2], and interfere with other pro-apoptotic proteins [3], E7 interacts with the PDZ domain of cellular proteins, such as retinoblastoma protein (pRb) to cause cellular transformation, leading to neoplastic progression [4]. Previous studies have revealed that LncRNAs (long non-coding RNAs), which are non-coding transcripts that are more than 200nt in length, are important regulators in various biological processes such as proliferation, differentiation and metastasis, and took vitally an function on the oncogenesis and progression of cervical cancer [5]. It was revealed that there was a close correlation between HPV16 E7 and LncRNA HOTAIR expression in cervical cancer, whereas the detailed mechanism was not identified [6]. So far, the mechanism by which LncRNAs are regulated in cervical cancer is mainly obscure. As an important causative factor of cervical cancer [7], demonstrating how high-risk HPVs regulated the expression of cancer-related LncRNAs would help to understand the mechanism of cervical cancer development.
X. Liu Y. Lai H. Yao M. Zhang H. Zhou T. Zhang H. He (&) Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, People’s Republic of China e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2018 H. Liu et al. (eds.), Advances in Applied Biotechnology, Lecture Notes in Electrical Engineering 444, https://doi.org/10.1007/978-981-10-4801-2_74
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Through a review of literatures regarding LncRNAs associated with various malignant tumors [8], particularly cervical cancer [9], we selected 11 LncRNAs, including 9 previously reported ones MALAT1 [10], TMPOP2 [11], TUSC8 [12], H19 [13], UCA1 [14], CRNDE [15], GAS5 [16], NPTN-IT1 and MEG3 [17], and two function-unknown ones Lnc-01468 and Lnc-00657, for investigation in the present study. MALAT1, TMPOP2, UCA1, H19 and CRNDE which were up-regulated in cervical cancer compared with adjacent tissues were proposed to be correlated with the size, FIGO stage, vessel invasion, lymphatic diffusion, and other features of cervical cancer. TUSC8, GAS5, NPTN.IT1 and MEG3 were reported to be downregulated in cervical cancer, and may play a role in tumor suppression. Lnc-01468 and Lnc-00657 are newly identified LncRNAs with unknown function in cervical cancer. The expression of these 11 LncRNAs in HeLa, a cervical cancer cell line carrying HPV18 DNA in cellular genome, was measured with RT-qPCR method and a comparison was made between HeLa and HaCaT, a nonmalignant epithelial cell line. Addition
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