Cervical cancer is the fourth most common malignancy in women and one of the leading causes of cancer deaths in women, accounting for nearly 7.5% of female cancer deaths worldwide [1]. The incidence and mortality rates of cervical cancer in developed countries have gradually decreased. However, in less developed countries, cervical cancer is still one of the most common malignant tumors in women and one of the main causes of death due to malignant tumors [2], [3]. According to histopathology, cervical cancer can be divided into cervical squamous cell carcinoma, cervical adenocarcinoma and other rare types such as adenosquamous carcinoma, neuroendocrine carcinoma and smooth muscle sarcoma. Among them, the most common type of cervical cancer is cervical squamous cell carcinoma (CESC), which accounts for about 80% of the total number of cases [4], [5], [6]. Although patients with early-stage cervical cancer have a good prognosis. However, for advanced cervical cancer, cisplatin-based chemotherapy is preferred, but its efficacy is unsatisfactory, with only 1 in 5 patients responding to cisplatin-based chemotherapy modalities or radiotherapy-chemotherapy combinations [7], [8]. Therefore, exploring the mechanism of the development of CESC, finding new prognostic molecules and effective target molecules for early diagnosis and establishing new effective therapeutic measures for CESC are the urgent clinical issues to be addressed.

B-cell translocation gene 2 (BTG2) is located on chromosome 1q32 and is a member of the antiproliferative BTG/TOB gene family. The BTG/TOB family has been shown to contain six members divided into two distinct subfamilies, BTGs (BTG1–4) and TOBs (TOB1–2) [9]. BTG2 is the first protein identified in the BTG/Tob protein family. Amino acid sequence similarity indicates that BTG1 and BTG2 are highly similar. The antiproliferative (APRO) structural domain is a key conserved structural domain in both BTG1 and BTG2. In BTG1 and BTG2 is the conserved APRO structural domain that contains three motifs: Box A, Box B and Box C. These boxes make it easier for the proteins to interact with each other [10]. BTG1 and BTG2 functions affect major biological processes. Expression of BTG1 and BTG2 induces cell cycle arrest in the G1 phase. BTG2 also promotes DNA damage-induced G2/M block. Expression of BTG1 and BTG2 is essential for differentiation in a variety of tissues, including neurons and the axial skeleton. DNA damage can cause programmed cell death via BTG1 and BTG2. BTG2 is a downstream effector of ROS and NF-κB to overcome oxidative stress [11]. BTG2 is involved in a variety of biological processes such as cell cycle, cellular senescence, cell differentiation hematopoiesis, oxidative damage, gene transcription and DNA damage repair [11], [12]. Downregulation of BTG2 expression plays a crucial role in tumor development, and BTG2 downregulation is associated with poor prognosis in cancers such as esophageal squamous cell carcinoma, breast cancer, hepatocellular carcinoma and bladder cancer, and BTG2 is considered as a potential tumor-suppressor [13], [14], [15], [16], [17], [18]. However, the expression and molecular function of BTG2 in CESC are unknown.

In this study, firstly, we evaluated the expression of BTG2 in the tissues of CESC patients and explored its impact on patient prognosis and survival. Secondly, we investigated the effect of BTG2 on the proliferation and metastasis of CESC cells by cellular assays. Finally, we confirmed the effect of BTG2 on CESC tumors in vivo by tumorigenic assay in nude mice. In conclusion, this study reveals an undefined role of BTG2 in CESC and provides new ideas for the prognosis prediction and clinical treatment of CESC patients.