Gastric cancer is a multifactorial disease with a complex interplay between genetics, lifestyle, and environment [28,29,30,31]. Helicobacter pylori infection is the most common chronic bacterial infection and affects over 50% of the world’s population. It is a major cause of gastritis and gastric ulcers, and gastric cancer [32,33,34]. Recent gene profiling studies identified a link between miRNAs and gastric-related disease. Compared to healthy individuals, miRNA expression was significantly different in patients with chronic gastritis and gastric cancer [2]. Gastric cell lines with elevated miR-223 levels displayed a significant reduction in apoptosis. miR-223 overexpression also activated gastric cancer cell proliferation and invasion. Overall, miR-223 may play a crucial role in tumor progression and the survival of gastric cancer cells. As a result, miR-223 is proposed as an oncogene for gastric cancer [27]. As such, miR-223 expression can assist in the diagnosis and treatment of gastric cancer [27].

The mechanism responsible for increased gastric carcinogenesis was reported by Li et al., 2011. Their work demonstrated that miR-223 binds to FBXW7/hCdc4 at the 3′-UTR region of FBXW7/hCdc4 mRNA. The FBXW7/hCdc4 gene is a well-established p53-dependent tumor suppressor gene that encodes an ubiquitin ligase involved in chromosome stability. FBXW7 is a commonly deregulated ubiquitin-proteasome system protein in human cancers. As follows, miRNA-223 downregulation of FBXW7/hCdc4 is involved in gastric tumorigenesis due to increased genetic instability. In summary, miR-223 exerts its carcinogenic role by downregulating FBXW7/hCdc4 expression. This outcome rationalizes micrRNA-223 as a novel therapeutic target for gastric cancer [2,27].

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide, and the number of cases and deaths is predicted to increase [35]. HCC patients showed significantly higher miR-223 levels compared to healthy individuals. As a result, miR-223 is proposed as a potential diagnostic biomarker for HCC. However, tissue injury, more than carcinogenesis, is implicated in miR-223 overexpression for hepatocellular disorders. Hepatitis B patients with HCC-negative results showed higher serum levels of miR-223 compared to HCC and healthy subjects. Chronic hepatitis patients displayed greater hepatocyte damage compared to HCC patients, and hepatitis (tissue injury) likely leads to elevated miRNA-223 serum levels rather than HCC [36].

Breast cancer is a major cause of mortality among women in developed and developing countries (IARC, 2008) [37,38]. Its incidence is continuing to increase, likely due to early screening and its public health emphasis, along with other factors [39,40]. According to Gong et al., breast cancer cells (MDA-MB-231) express abnormally low levels of miR-223 and abnormally high levels of Caprin-1. Caprin-1 overexpression promotes proliferation and invasion of breast cancer cells. Conversely, miR-223 expression inhibits breast cancer cell proliferation and invasion in MDA-MB-231 cell lines [41]. miR-223 targets 3′-UTR of Caprin-1 mRNA and downregulates Caprin-1 expression. A decrease in miR-223 biogenesis likely reduces Caprin-1 regulation. Caprin-1 deregulation then results in greater carcinogenesis in breast cancer cell lines, such as MDA-MB-231 [41]. In summary, miR-223 may suppress proliferation and invasion of breast cancer cells by directly targeting Caprin-1. As a result, miR-223 and Caprin-1 expression can be used predictively in cancer diagnosis and prognosis [41].

Lung cancer is an aggressive disease, particularly when considering its high incidence and mortality rates [42]. Consequently, novel therapeutic biomarkers are needed to improve disease outcomes [43]. Disease progression displays a negative correlation between miR-223 expression and lung cancer development and metastasis [44,45,46]. According to Nian et al., miR-223 functions as a potent tumor suppressor by targeting IGF-1 receptor and cyclin-dependent kinase 2. Low miR-223 serum levels are associated with high cancer-related death. As a result, miR-223 can be used as an early diagnostic and therapeutic biomarker to improve the treatment of lung cancer [22].

Ovarian cancer is a heterogeneous disease that encompasses a number of different cellular subtypes. The most common subtype is high-grade serous ovarian cancer (HGSOC). HGSOC is also the most lethal of all gynecologic malignancies diagnosed in the United States [47]. Recent advances have been unable to significantly improve patient outcomes. In the last 20 years, patient survival at 5 years post-diagnosis has marginally improved to 46% from about 35–38% [48].

miR-223-3p expression is upregulated in ovarian cancer. In this context, miR-223 decreases sex-determining region Y-box 11 (SOX11) expression. Inhibiting the sox11 gene negatively regulates cell proliferation, migration, and invasion. Accordingly, a therapeutic target of miR-223-3p can potentially regulate ovarian cancer by targeting SOX11 expression [48].

Osteosarcoma is a bone tumor malignancy in adolescents and young adults [49]. miR-223 is downregulated in osteosarcoma [50,51]. Xu et al. reported that upregulation and downregulation of miRNA-223 lead to significantly diminished and enhanced cell proliferation and cell cycle progression in osteosarcoma, respectively. Thus, miR-223 is proposed as a therapeutic biomarker for osteosarcoma [51].

miRNA dysregulation is frequently observed in colon cancer [52]. Previous studies found that the miR-223 oncogene is upregulated in colon cancer [53,54]. In 2017, Liu et al. proposed that miR-223 promotes colon cancer invasion and metastasis by downregulating p120, which reduces intercellular adhesion, promotes RhoA activity, and activates β-catenin signaling [53,55]. As a result, miR-223 is a potential diagnostic and therapeutic target for anti-colon cancer treatment. It was reported that miR-223 functions as an oncomiR in T cell acute lymphoblastic leukemia, whereas in acute myeloid leukemia (AML), it functions as a tumor suppressor [56,57,58]. According to Gao et al., low expression of miR-223 has been found in various human hematologic malignancies and solid tumors, where it acts as a tumor suppressor, and has a significant role in leukemia and lymphomas. miR-223 significantly inhibits the proliferation, growth rate, and colony formation of cells in vitro, and tumor formation in vivo through targeting IGF-1R and its downstream PI3K/Akt/mTOR/p70S6K pathway in leukemia [57,59,60]. Compared with normal tissues, miR-223 is also upregulated within the cancerous tissues of pancreatic, gastric, and prostate cancer biopsies [55,61]. In a study by Wei et al., miR-223 promoted prostate tumor development and malignancy by decreasing cell apoptosis and increasing cell migration. These effects were reversed by upregulating SEPT6. As a gene target of miR-223, SEPT6 is downregulated by miR-223 overexpression. Consequently, SEPT6 can serve as a potential therapeutic target for prostate cancer [62].

Hepatocellular carcinoma (HCC) displays a high recurrence rate. This common reoccurrence requires further investigation into diagnostic and therapeutic targets for HCC treatment [92]. miR-223 overexpression was reported in patients with either HCC or chronic hepatitis B. The usefulness of miR-223 as a diagnostic biomarker for HCC is limited by its shared miR-223 profile. Chronic hepatitis B also displays elevated miR-223 levels; however, this overexpression is caused by inflammation and liver injury, not the presence of hepatocellular carcinoma [36,93,94].

According to Karakatsanis et al., miR-223 downregulation inhibits HCC cell growth, suggesting that miR-223 plays an important role in HCC progression and metastasis [94] Moreover, it was reported that miR-223-3p could be used as a promising prognostic biomarker as circulating miR-223-3p significantly differentiates HCC from the non-HCC groups [95]. Consequently, further investigation of miR-223 is essential.

Escobar et al. highlighted the effects of macrophages and miRNA on breast cancer cells. miR-223 overexpression, coupled with high levels of macrophage infiltration, results in an aggressive cancer phenotype [91]. In 2018, Yang et al. showed that miR-223 inhibits the proliferation and invasion of breast cancer by targeting STIM1 [96]. According to Chen et al., high expression of miR-223 acts as a tumor suppressor, which is correlated with prolonged survival in triple-negative breast cancer patients. Hence, miR-223 could be an independent prognostic biomarker in breast cancer [97]. As reported, miR-223 can serve as a potential diagnostic biomarker for breast cancer [91,96].

Esophageal cancer is a leading cause of cancer-related deaths worldwide. Most physicians recommend surgical resection for esophageal carcinomas at their early stages [98]. Due to the limited treatment options, further research is needed to identify biomolecular pathways involved in esophageal cancer malignancy [90,98,99].

Artemin (ARTN) is a growth factor associated with the tumorigenesis and progression of human cancers. ARTN also promotes cell migration, invasion, and metastasis [99,100,101]. After chemotherapy, artemin expression is strongly correlated with relapse and death in carcinoma patients [102,103].

According to Wu et al., miR-223 directly binds the ARTN 3′-UTR and regulates ARTN protein expression [102]. ARTN function is suppressed by miR-223 overexpression, which reduces esophageal cancer cell migration and invasion. In contrast, ARTN upregulation via miR-223 silencing promotes cell migration and invasion [102]. These observations rationalize microRNA-223 and artemin as therapeutic targets for esophageal cancer treatment.

In lung cancer, like all cancers, early diagnosis promotes favorable patient outcomes [103]. As a result, the identification of novel early diagnostic biomarkers related to tumorigenesis is vital for future advancements in cancer diagnosis and treatment [43].

miR-223 targets IGF-1R, a transmembrane receptor tyrosine kinase related to lung cancer oncogenesis, tumor growth, and cancer cell survival [103]. IGF-1R upregulation is involved in the initial dysregulation that shifts previously healthy cells towards tumorigenesis and malignancy. In contrast, IGF-1R downregulation sensitizes lung cancer cells to chemotherapy and radiation by inhibiting cell proliferation. As reported, miR-223 overexpression leads to tumor suppression in lung cancer [103]. According to Antona et al., miR-223 could be an early-stage serum biomarker for non-small cell lung cancer (NSCLC). Moreover, miR-223 is considered as an effective and reproducible serum biomarker [104]. Overall, miR-223 targets IGF-1R and its downstream signaling pathway for downregulation, leading to inhibited cell growth and proliferation [74]. Targeting miR-223 for overexpression could be a good strategy for lung cancer treatment.