As one of the most common cancers in the world, colon cancer ranks fifth in cancer-related mortality [1]. According to statistics, there are 1.2 million new cases and 600,000 deaths from colon cancer worldwide every year [2]. In recent years, blocking key genes to regulate malignant transformation has become an effective approach to control tumors [3], [4]. Over the past decade, miRNAs have frequently been used as potential candidates for studying cancer progression [5].

MiRNAs are short non-coding molecules found in both animal and plant cells, involved in regulating various cellular processes including cell migration, differentiation, and tumor growth [6], [7]. Growing evidence has proved that abnormally expressed miRNAs can affect the occurrence and development of various malignancies by regulating tumor-related genes. For instance, the overexpression of miR-203 has been demonstrated to inhibit cell growth by decreasing Rap1A expression in prostate cancer [8]. Therefore, dysregulated miRNAs may provide clues for cancer progression therapy.

Numerous studies have reported that dysregulation of miR-129-2-3p can lead to tumor cell proliferation, cycle arrest, and migration by regulating the expression of oncogenes or tumor suppressor factors [9], [10]. For example, miR-129-2-3p inhibited malignant behaviors of esophageal carcinoma by targeting DNMT3B [9]; MiR-129-2-3p inhibited the breast cancer cell proliferation via regulation of BCL2L2 [11]. However, the regulatory function of miR-129-2-3p in colon cancer cells is not completely understood.

The basic leucine zipper and W2 domain 1 (BZW1), also known as BZAP45, primarily encodes a 45 kDa protein [12]. Previous studies have demonstrated that BZW1 plays a crucial role in transcriptional activation of histone H4 gene at the site II [12]. Recently, overexpression of BZW1 has been identified as an independent prognostic marker of poor prognosis, and its upregulation promotes lung cancer metastasis [13]. However, the exact role of BZW1 in the pathogenesis of colon cancer remains unclear. In this study, we identified BZW1 as a potential target gene of miR-129–2 through bioinformatics analysis.

In our work, we transfected with miR-129-2-3p mimic in colon cancer cells and conducted a series of analyses, including CCK-8, colony formation, flow cytometry, wound healing, Transwell assays, to explore the role of miR-129-2-3p on malignant phenotype of colon cancer cells. Moreover, we performed dual-luciferase reporter assay to identify the target of miR-129-2-3p. We found that basic leucine zipper and W2 domain 1 (BZW1) is a direct target of miR-129-2-3p. Finally, we investigated the role of miR-129-2-3p in the tumor microenvironment by injecting Lovo cells with miR-129-2-3p overexpression into the xenograft mice.

The intent was to investigate whether miR-129-2-3p can exert a suppressive effect in colon cancer through the regulation of BZW1. Additionally, our research will provide new insights for the treatment of colon cancer.