The roles of RUNX3 in cervical cancer cells in�vitro

Abstract

Abstract. RUNX3 serves an important role in development of various types of human cancer. The purpose of the present study was to investigate the potential biological function of RUNX3 in cervical cancer cells. In the present study, a RUNX3 overexpressed model was constructed in Hec1 cells by PCDNA3.1-RUNX3 transfection. Western blot analysis was used to measure RUNX3 expression in cervical cancer cells. Immunofluorescence analysis was performed to examine subcellular localization of RUNX3 in cervical cancer cells. Effects of RUNX3 expression on proliferation, migration and invasion of cervical cancer cells were detected by colony formation assay, wound healing assay and Transwell assay, respectively. Immunofluorescence confirmed the nuclear location of RUNX3 in cervical cancer cell. Result sindicated that upregulation of RUNX3 expression inhibited proliferation, migration and invasion of cervical cancer cells. However, knockdown of RUNX3 expression promoted the proliferation, migration and invasion of cervical cancer cells. Hence, RUNX3 may serve as a tumor suppressor gene in cervical cancer. IntroductionCervical cancer is one of the most common malignancies in women. The incidence is second only to that of breast cancer, which also poses a serious threat to women's health (1). In recent years, one study found that the continuous upgrading of screening methods and the popularity of the human papillomavirus vaccine had caused the incidence of both cervical cancer cases and mortality to decline. Due to the uneven distribution of resources, the incidence is still rising in developing countries, and the trend may affect younger patients (2). As molecular biology research becomes more sophisticated, more and more genes have been found to be involved in the development of cervical cancer. Finding new molecular targets for the prevention and treatment of cervical cancer could have far-reaching implications.The RUNX3 tumor suppressor gene was discovered a few years ago. With RUNX1 and RUNX2, it makes up the transcription factor RUNX family (3). RUNX1 is associated with hematopoietic function (4), and RUNX2 is an important bone formation regulator (5). RUNX3 is located on chromosome 1p36.1 and contains a p1 promoter and p2 promoter (6). Alkaline phosphatase (ALP), a marker of BMP9-induced late osteogenic differentiation was enhanced by the overexpression of RUNX3, whereas it was inhibited by the knockdown of RUNX3 (7). It was first reported to be a tumor suppressor gene in gastric epithelial cells (8), and it was also reported to absent or mutated in a variety of cancers for hemizygous deletions (9), protein mislocalization, epigenetic alterations (10), and histone modifications (11). Suzuki et al (12), initially described the DNA promoter of RUNX3 hypermethylation as a characteristic of breast cancer. Paradoxically, with the discoveries reported by Nevadunsky et al (13) and Lee et al (14), found that RUNX3 took on a growth-stimulating role, which was highly active in ovarian cancer cells, likewise, it even played an o...

Transcriptome changes induced by RUNX3 in cervical cancer cells in�vitro

“…In the present study, the upregulated expression of RUNX3 consistently inhibited the proliferation and promoted the apoptosis of cervical cancer cells, particularly in the SiHa cell line. The results were similar to those of a recent study on cervical cancer, which reported that upregulated expression of RUNX3 inhibited the proliferation, migration and invasion of cervical cancer cells (12). According to these results, it may be concluded that RUNX3 acts as a tumor suppressor gene in cervical cancer (12).…”

“…In the present study, three types of cervical cancer cell lines were selected: SiHa, HeLa and C33A, infected by HPV-16, HPV-18 or not infected, respectively. It was recently reported that RUNX3 may play a key role in the development and progression of cervical cancer (12). It was also observed in the present study that RUNX3 may inhibit cervical cancer cell proliferation, particularly in the SiHa cell lines, indicating its potential function as a tumor suppressor; inconsistencies in these results may be due to the different cell lines.…”

“…In a number of previous studies on gastric, hepatocellular and breast cancer, RUNX3 has been revealed to play a significant role in tumor suppression (8–11). Recent research has demonstrated that RUNX3 may also act as a tumor suppressor gene in cervical cancer (12). RUNX3 expression may be suppressed by promoter hypermethylation, gene deletions, inactivating mutations and protein mislocalization (8,11,13–16).…”

MicroRNA‑130a‑3p promotes the proliferation and inhibits the apoptosis of cervical cancer cells via negative regulation of RUNX3

“…runX3 is mapped on human chromosome 1p36, and has been reported to serve as an anti-tumor gene in lung (31), bladder (32) and gastric cancer (33). li et al (21) revealed that knockdown of runX3 promoted the proliferation, migration and invasiveness of cc cells. Similarly, Gao et al (34) reported that upregulation of runX3 inhibited the proliferation of cc cells.…”

“…runX3 may also have a major role in the cellular processes of tumorigenesis and metastasis, including epithelial-mesenchymal transition (eMT) (17), adhesion (18), invasion (19) and apoptosis (20). Zhen et al (21) revealed that overexpression of runX3 suppressed the proliferation, migration and invasion of cc cells, thus suggesting that runX3 may function as a tumor suppressor in cc. However, the regulatory relationship between mir-130a-3p and runX3 in cc remains unclear.…”