Transmembrane protein 160 (TMEM160) is involved in cell proliferation and migration in lung and cervical cancer

INTRODUCTION. Transmembrane protein 160 (TMEM160) is localized to the mitochondrial membrane and is predicted to also localize to the nucleus, peroxisome membrane, and endoplasmic reticulum. It has been reported that in humans its expression is found in more than 200 tissues. It has been suggested that TMEM160 may suppress the generation of reactive oxygen species and stabilize mitochondrial proteins. In recent years, it has been reported that TMEM family proteins play roles as oncogenes or tumor suppressor genes. It is unknown if TMEM160 plays a role in cancer, we identified that it is overexpressed in the cell lines A549 of lung adenocarcinoma and HeLa of cervical adenocarcinoma, so we are interested in identifying the role that TMEM160 plays in lung cancer and cervical cancer.

METHODOLOGY. To investigate the role of TMEM160 in cancer, we employed a variety of techniques. First, we silenced the TMEM160 gene using CRISPR/CAS9 in A549 and HeLa cell lines. We then conducted proliferation, migration, and invasion assays in wildtype (WT) and knockout (KO) cells. In vivo experiments involved xenografting mice with WT and KO cells. To gain further insight, we co-immunoprecipitated TMEM160 in protein extracts from A549 and HeLa cell lines using LC-MS/MS. Pathway enrichment analysis was performed to understand the processes involving TMEM160 and its partners. Finally, we used immunofluorescence to identify the subcellular localization of TMEM160.

RESULTS. TMEM160 shows higher expression in the A549 cell line versus the BEAS cell line (non-tumor bronchial epithelium) and in the HeLa cell line compared to HaCaT (non-tumor keratinocytes). In addition, TMEM160 knockout decreases cell proliferation and migration in vitro and in vivo in lung cancer and cervical cancer cells. It was identified that in co-immunoprecipitations in A549 cells, TMEM160 interacts with importins that mediate the entry of proteins into the nucleus. Likewise, the cellular processes that were enriched were DNA replication and spliceosome. By immunofluorescence we observed that TMEM160 has cytoplasmic and nuclear localization.

CONCLUSIONS. This study provides an initial understanding of the function of TMEM160 in cancer cells. Our findings indicate that the absence of the protein in A549 cells significantly reduces cell proliferation and migration. Moreover, we discovered a novel interaction between TMEM160 and nuclear importins, shedding light on a potential mechanism in cancer progression.