Identiﬁcation and functional analysis of a novel splice variant of AC3‑33 in breast cancer

Yuan,Lu; Hu,Fen; Zhang,Yunfeng; Meng,Lijun; An,Tianyang; Chen,Yajing; Zhang,Xiujun

doi:10.3892/etm.2019.8212

Identiﬁcation and functional analysis of a novel splice variant of AC3‑33 in breast cancer

Authors:
- Lu Yuan
- Fen Hu
- Yunfeng Zhang
- Lijun Meng
- Tianyang An
- Yajing Chen
- Xiujun Zhang
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Affiliations: College of Public Health, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China, Department of Environmental and Chemical Engineering, Tangshan College, Tangshan, Hebei 063000, P.R. China, College of Jitang, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, College of Pharmacy, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, College of Psychology, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China
Published online on: November 18, 2019 https://doi.org/10.3892/etm.2019.8212
Pages: 183-191
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Alternative RNA splicing plays a key role in regulating gene function and influencing protein expression diversity. In the present study, an AC‑33 transcript variant (NCBI Reference Sequence: NM_001308229.1), splice variant (sv)AC3‑33, was successfully cloned from the MCF‑7 breast cancer cell line by reverse transcription PCR using primers based on expressed sequence tags. The aim of the present study was to investigate the structure and function of svAC3‑33. svAC3‑33 has an open reading frame of 1,825 base pairs, lacks AC3‑33 exon 2 and is encoded by 294 amino acids. svAC3‑33 is localized within the cytoplasm. The Cell Counting Kit‑8 and EdU detection of cell proliferation assays showed that svAC3‑33 inhibited MCF‑7 cell proliferation. Similarly, svAC3‑33 knockdown by RNA interference was shown to have the opposite effect by repressing the cell cycle progression of breast cancer cells. Furthermore, the data indicated that svAC3‑33 may upregulate the expression of p21. The present study provides evidence that the increased expression of svAC3‑33 may inhibit the activity of the transcription factor AP‑1. The luciferase reporter gene assay detected a downregulation of the expression of c‑Jun, but not c‑Fos, which in turn affected cell proliferation. In conclusion, these results indicated a function for svAC3‑33 in inhibiting the cell proliferation of MCF‑7 cells by regulating the AP‑1 signaling pathway.

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