Transmembrane protein 121 as a novel inhibitor of cervical cancer metastasis

Yang,Boyu; Cai,Yi; Zhu,Ping; Jiang,Zhigang; Ao,Jieyu; Zhang,Qing; Yuan,Wuzhou; Peng,Zhilin; Chen,Jimei; Wen,Yao; Chen,Yu; Wang,Yuequn; Shi,Yan; Zhu,Xiaolan; Ye,Xiangli; Li,Fang; Zhuang,Jian; Wu,Xiushan; Li,Yongqing; Fan,Xiongwei

doi:10.3892/etm.2022.11509

Transmembrane protein 121 as a novel inhibitor of cervical cancer metastasis

Authors:
- Boyu Yang
- Yi Cai
- Ping Zhu
- Zhigang Jiang
- Jieyu Ao
- Qing Zhang
- Wuzhou Yuan
- Zhilin Peng
- Jimei Chen
- Yao Wen
- Yu Chen
- Yuequn Wang
- Yan Shi
- Xiaolan Zhu
- Xiangli Ye
- Fang Li
- Jian Zhuang
- Xiushan Wu
- Yongqing Li
- Xiongwei Fan
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Affiliations: State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, P.R. China, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510100, P.R. China
Published online on: July 15, 2022 https://doi.org/10.3892/etm.2022.11509
Article Number: 572
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transmembrane protein 121 (TMEM121) is isolated from the chicken heart using subtraction hybridisation. A previous study by the authors indicated that TMEM121 is highly expressed in adult mouse hearts and acts as an inhibitor of pathological cardiac hypertrophy. In the present study, the association between TMEM121 and cancer was investigated using bioinformatics tools, including Tumour Immune Estimation Resource (TIMER) 2.0, cBioPortal, LinkedOmics analysis, Kaplan‑Meier plotter and UALCAN analysis. The expression, genetic variation, gene interaction network and co‑expression pattern of TMEM121 in tumours were analysed. The results revealed that TMEM121 was expressed in various tumours and significantly downregulated in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) when compared with its expression in paracancerous tissues, whereas the methylation level of its promoter was increased in tumour tissues. Additionally, associations between TMEM121 and the PI3K/AKT signalling pathway, as well as the expression of cancer‑related molecules, were detected. The aforementioned bioinformatics analysis suggests that TMEM121 may be involved in the development of cervical cancer. Therefore, gain‑of‑function and loss‑of‑function experiments in HeLa cells were conducted to verify the role of TMEM121 in cervical cancer. The assay using Cell Counting Kit‑8 (CCK‑8) revealed that the cell viability of HeLa cells with TMEM121 overexpression was significantly reduced. High TMEM121 expression inhibited HeLa cell migration, as indicated by the decrease in the cell scratch healing rate. The western blot assay revealed that TMEM121 overexpression downregulated the expression of B‑cell lymphoma 2 (BCL‑2), cyclin D1, cyclin E2 and phosphorylated (p)‑AKT, while upregulating that of p27, E‑cadherin and p‑p38. When TMEM121 was knocked down, retinoblastoma protein (RB), p53, p27, E‑cadherin, p‑JNK and p‑p38 were inhibited, but cyclin E1 was promoted. By combining bioinformatics and experimental biology in the present study, the results demonstrated for the first time, to the best of our knowledge, that TMEM121 may be a novel inhibitor of cervical cancer that is linked to multiple signalling pathways, paving the way for the development of novel diagnostic and therapeutic strategies.

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