Published online Feb 24, 2024. doi: 10.5306/wjco.v15.i2.302
Peer-review started: September 15, 2023
First decision: October 17, 2023
Revised: October 20, 2023
Accepted: November 27, 2023
Article in press: November 27, 2023
Published online: February 24, 2024
Processing time: 157 Days and 22.8 Hours
Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins that was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear.
Previous studies have identified TM9SF1 expression in BC, and through genome-wide microarray analyses of tissue sections, TM9SF1 has been found to be a commonly differentially expressed gene in BC. However, the biological function of TM9SF1 in BC cells remains unclear. To discover better treatment options for this disease, it is crucial to conduct a more in-depth exploration of its biological behavior.
This study explored the effect of TM9SF1 on BC cells’ biological phenotype by constructing stable cell transfectants with overexpression or silencing of TM9SF1. The biological relationship between TM9SF1 and BC in vitro was validated, with an aim to provide a new way of thinking about targeted BC therapy.
Cells at 60%-80% confluence were transfected with lentiviral vectors to achieve stable overexpression or silencing of TM9SF1 in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry.
In this study, we confirmed that TM9SF1 is a pro-carcinogenic gene in BC by overexpressing and silencing it in the 5637, T24, and UM-UC-3 cell lines using cellular function assays. The experimental results of the present study revealed that overexpression of TM9SF1 reduces the number of cells in the G1 phase and prompts them to enter the G2/M phase and start mitosis, thereby promoting BC cell proliferation. Yet, the silencing of TM9SF1 blocks cells in the G1 phase and prevents them from entering the DNA replication phase, thereby inhibiting BC cell proliferation. It is hypothesized that TM9SF1 may promote BC cell proliferation mainly by affecting the cell cycle progression of BC cells, which in turn promotes BC development.
This study was the first to attempt to construct a stable BC cell line to investigate the overexpression and silencing of TM9SF1 using in vitro experiments for the purpose of exploring the pro-cancer effect of TM9SF1 in BC. We verified that overexpression of TM9SF1 enhances the growth, migration, and invasion of BC cells and promotes their entry into the G2/M phase of the cell cycle. TM9SF1 may be an oncogene in BC.
In addition to influencing the biological phenotype of BC and promoting its development, TM9SF1 may also impact the anti-tumor immune response in BC. Further research is needed to elucidate the mechanisms underlying this effect. Furthermore, genetic factor analysis and targeted therapy aimed at inhibiting carcinogenesis offer promising prospects.