In 2020, the incidence of colorectal cancer (CRC) represented 10% of the total cancer cases reported globally, with 9.40% mortality. Furthermore, by 2040, 3.20 million new CRC cases are expected worldwide. Although CRC ranks third in prevalence, its alarming mortality is only second to lung cancer (18%) [1]. Poor diet, inadequate exercise, heavy alcohol use, and smoking are among the preventable risk factors that are responsible for more than half of all CRCs [2]. Since these behaviors are often associated with high-income nations, this explains high CRC incidence rates [3]. The risk of CRC is lowered by 27%− 52% in those who maintain a healthy lifestyle, according to several studies [4].

Since precancerous polyps gradually develop into invasive cancer and end-stage sickness, they provide a unique chance for CRC prevention and early diagnosis. To prevent the spread of cancer to other parts of the body following surgery, chemotherapy is often used as either the main therapy or as an adjuvant treatment. Unfortunately, chemotherapy has certain unpleasant side effects and the development of chemoresistance may limit its usefulness [5], [6]. Screening may reduce the prevalence of cancer, improve patients' chances of surviving, and allow for more effective treatment [7], [8]. Among the numerous possible biomarkers for screening, microRNAs (miRNAs) have emerged as new prognostic, therapeutic, and diagnostic markers in patients with CRC [9].

Treatment options for CRC include neoadjuvant chemotherapy, adjuvant therapy, and chemotherapy for incurable or recurring patients. Drugs often used for the treatment of CRC have received FDA approval[10]. To enhance surgical treatment, neoadjuvant chemotherapy, adjuvant chemotherapy, and radiation are being used for patients with advanced CRC [11]. Patients with locally advanced CRC may receive radiotherapy either as adjuvant therapy after surgery to prevent recurrence or as preoperative therapy to reduce tumor volume and preserve the anal sphincter. Additionally, patients with unresectable CRC who have symptomatic lesions may receive radiotherapy as palliative care to relieve their symptoms and prolong their survival time. Radiotherapy is used for the treatment of patients with regionally progressed CRC [12].

miRNAs are small, noncoding RNA sequences that modify gene expression by affecting the integrity or translation efficiency of messenger RNAs [13]. These sequences are found across the genome in exonic, intronic, and intergenic regions [14], [15]. Both the nucleus and the cytoplasm play roles in the complex multi-step process of miRNA production from its genomic loci (Fig. 1). miRNAs have a negative role in gene regulation by binding to a specific sequence on mRNA (3′ UTR), coding sections, or 5′ UTR, resulting in mRNA degradation or inhibition of translation [16]. miRNAs control several biological activities, including cell proliferation, cell cycle, and apoptosis regulating numerous crucial biological activities [17]. The biological significance of miRNAs exploited their ability to target oncogenes or tumor suppressor genes in different types of cancers [9], [13], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], liver diseases [38], bone diseases [39] metabolic syndrome [40], [41], [42], rheumatoid arthritis [43], and diabetes [44], [45], [46], [47].

Many miRNAs are associated with CRC in which their overexpression accelerates progression and growth, such as miR-574–5p [48], miR-188–5p [49], and miR-23b/ 27b/24 [50]. In contrast, some miRNAs inhibited cancer growth, such as miR-133a [51], miR-326 [52], and miR-485–5p [53].

The miR-509–5p gene is located on chromosome Xq27.3 and encodes miR-509–5p [54]. According to the literature review, it plays a critical function in the carcinogenesis and development of many cancer types, such as renal cell carcinoma (RCC) [55], cervical [56], NSCLC [57], and breast [58]. Despite this, the biological role, as well as molecular mechanisms underlying miR-509–5p effect in CRC development and growth control, warrant more investigation.

Ferroptosis is an unusual type of programmed cell death, in which lipid-derived reactive oxygen species (ROS) accumulate and cause damage to cells [59], [60]. Although it may seem similar to autophagy, apoptosis, and necrosis, it is mainly characterized by iron overload, which increases free radical production and lipid peroxidation [61]. Recent research shows a causal link between ferroptosis and the development of CRC. As a result, ferroptosis induction may be beneficial for inhibiting the growth and progression of CRC [62]. These results justify investigating ferroptosis as a potential therapeutic target for CRC.

Solute carrier family seven-member 11( SLC7A11) is a crucial element of the Xc- system, essential for transporting extracellular cysteine, a precursor for the production of glutathione (GSH) within cells [63], [64]. The protein plays a crucial role in preventing ferroptosis during cancer onset and growth by regulating cysteine transport [65]. SLC7A11 is overexpressed in several tumors and regulates the absorption of extracellular cystine in exchange for glutamate at a 1:1 ratio. SLC7A11 has been demonstrated to have a variety of functions in tumors, both functionally and pharmacologically, including in cellular redox homeostasis, cell proliferation and death, and metabolism [66]. Many studies have found that suppressing SLC7A11 expression and activity is helpful in tumor therapy, so this protein is now considered a viable therapeutic target [67].

SLC7A11 is widely expressed in various tumor tissues, and miR-5096 overexpression can increase ferroptosis by targeting SLC7A11, resulting in the suppression of breast cancer growth [68]. Moreover, miR-375/SLC7A11 inhibits gastric cancer stem cells by triggering ferroptosis. Thus, miR-375 may induce ferroptosis in gastric tumor cells, leading to the suppression of cancer stem cell traits [69]. Potential options for therapy for colon adenocarcinoma include the possibility that SLC7A11 contributes to the induction of ferroptosis [70].

We hypothesize that miR-509–5p regulates SLC7A11 expression based on initial computational results identifying SLC7A11 as a potential target for this gene. This study investigated the potential association of miR-509–5p and SLC7A11 expression levels with CRC. Cellular and molecular function analyses were performed to evaluate the effects of miR-509–5p on CRC. The results demonstrate that miR-509–5p could suppress CRC tumor growth by targeting SLC7A11.