According to data [1], colorectal cancer is the second most significant cause of cancer-related mortality and the third most common cancer worldwide. The most popular method for identifying and screening colorectal cancer is colonoscopy. Nevertheless, it has downsides such intestinal preparation and the possibility of bowel rupture [2]. Over the past ten years, there have been significant advancements in CRC diagnosis and therapy. However, individuals with CRC may have a poor prognosis and a high death rate as a result of distant metastasis, particularly liver metastasis, and the cancer cells' cell stemness [3]. The (FIT) test has taken the position of the (gFOBT) test in the colorectal cancer screening procedure [4], [5], [6]. The threshold value for a positive result, however, determines how well the FIT performs as a diagnostic tool [7]. Blood-based indicators have an advantage over other markers because patient samples may be collected more conveniently and frequently [8]. New gene therapy approaches for administering therapeutic RNA, such as non-coding RNA or small interfering RNA (siRNA), have been the focus of recent investigations on the structure and function of non-coding RNAs in colorectal cancer. The molecular causes of CRC are of interest to researchers because of long non-coding RNAs (lncRNAs) [9], [10], [11], [12], [13], [14].

The novel type of circulating molecules that are attracting significant interest is miRNAs. MiRNAs are a subclass of non-coding regulatory RNA molecules with an average length of 22 nucleotides (nt), which typically bind to the 3′ UTRs of their target messenger RNAs to alter the expression of genes at the post-transcriptional level [15], [16], [17]. One miRNA may control up to 200 mRNAs, according to studies, which suggest that 1–4% of the human genome's genes encode miRNAs [18]. MiRNAs have a significant role in a variety of critical processes, including tissue differentiation, growth and proliferation of cells, embryonic development, and the procedure of apoptosis, according to the findings of several tests and studies [19]. MiRNAs have the distinct ability to be abundantly present in stable, functioning conditions in all biological circulating fluids, including plasma, urine, tears, and saliva [20]. As a result, miRNAs are potentially useful as biomarkers. Numerous miRNAs are implicated in the onset and prognosis of CRC, according to studies [21].

In numerous forms of human cancers, including tumors of the breast and lung tumors, miR-410 exhibits aberrant expression and functions as a tumor suppressor. As an interacting arm, CCDC144NL-AS1/hsa-miR-143–3p/HMGA2 correlated with CRC stages 2–4. Therefore, the expression of this clinically and in silico approved interaction arm will determine the accuracy of treatments in the near future. Other studies show that clinically and in silico confirmed lncRNA NNT-AS1/hsa-miR-485–5p/HSP90 axis expression (but not individually) in colorectal cancer may contribute to treatment accuracy. It has been shown. There is evidence that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are a promising group of non-protein-coding regulators for controlling the aggressiveness of various malignancies. Furthermore, both LINC00511 and miR-301a-3p were positively correlated with breast cancer aggressiveness. Therefore, these results contribute to the understanding of the pathogenesis of BC in clinical settings, which is partially related to LINC00511/miR axis, which could be a potential therapeutic target in the future.[22], [23], [24], [25]. Researchers claim that miR-410 controls FHL1, ITPKB, and Bak1 to efficiently regulate the biological activity of CRC cells [26], [27], [28], [29]. Additionally, miR-410 targets dickkopf protein 1 (DKK1), which helps to explain the miR-410/DKK1 pathway's underlying workings in CRC [30].

CRC pathogenesis is controlled by miR-215–5p, which inhibits metastatic growth. Various molecular pathways may be modulated by miRNAs, including extracellular matrix-receptor interaction, focal adhesion, Wnt signaling pathways, and stem cell pluripotency, to regulate CRC metastatic potential. However, certain targets of miR-215–5p must be identified in order to explain how they contribute to distant metastases and cancer development [31], [32].

Chromodomain-helicase-DNA-binding protein 5 (CHD5) belongs to a newly discovered tumor suppressor gene family [33], [34]. The expression of CHD5 is mostly suppressed in CRC [35], [36]. The researchers found that low CHD5 expression in colorectal cancer is related to hypermethylation of CHD5 promoter CpG islands. Using CHD5 expression as a model, they found miR-211 affected colorectal tumorigenesis [35], [37].

A tumor suppressor miR-328–3p is reported to be downregulated in various cancers. A large amount of evidence also indicates that miR-328–3p functions as a tumor suppressor miRNA in certain forms of human cancer: breast cancer, renal cancer, cervical cancer, gastric cancer, and Hodgkin lymphoma [38], [39], [40], [41], [42], [43].

The overexpression of miR-328–3p inhibits cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Overexpression of miR-328–3p also inhibited PI3K/Akt signaling [44], [45].

One of the critical molecules involved in regulating apoptosis is BCL2 [46]. To show experimentally that miR-129 controls BCL2 expression, the researchers performed experiments that revealed that miR-129 decreased BCL2 protein expression in all cell lines examined compared to negatively controlled miRNA [47], [48].

MiR-139–5p expression has been regulated by several mechanisms. The miR-139–5p promoter is activated by P53, inhibiting PDE4D and cAMP signaling and preventing cancer cell growth [49], [50].

CRC cells overexpressed with miR-139–5p were prevented from proliferating, migrating, and invading in vitro, made tumors more susceptible to chemotherapy, and deprived of the ability to grow and metastasize in vivo [51], [52].

miR197 has been shown to be a novel biomarker for various cancer types in a number of studies [53]. Many studies indicated that miR‑197 could be an oncomiR in cancer cell invasion and metastasis [54], [55]. By acting on CD82, miR-197 can play a vital role as a stimulus of invasion and migration in gastric and liver cancer via the EGFR-ERK1/2-MMP7 signaling pathway. Nevertheless, the various biological functions that miR-197 may perform in CRC are still unclear [56], [57].

LncRNAs (long non-coding RNAs) are transcribed by RNApol II and have lengths exceeding 200nt. There is no open reading frame (ORF) for them, so they cannot encode any proteins [58], [59]. The functions of lncRNAs are generally associated with chromatin modification, transcription, and post-transcriptional regulation. By interacting with chromatin remodeling complexes, lncRNAs cause heterochromatin to be created at specific genomic locations, which results in decreased gene expression.

In addition, lncRNAs can modulate transcription by interacting with coactivators and binders of RNA, or by modulating important promoters of their targets. As unique functional molecules, long noncoding RNAs communicate with DNA, mRNAs, short noncoding RNAs, and proteins in various cancer-related cellular activities serving as signals, decoys, scaffolds, and guides [60], [61], [62]. It has been demonstrated that lncRNAs play a key role in numerous CRC-related pathways as signaling molecules, as scaffolds for decoying CRC-specific protein partners, and as cis- and trans-regulatory elements for gene expression. CACS11, the CCAT family, and PVT1, for example, are oncogenic lncRNAs that promote CRC progression through their interactions with proteins to generate myc expression at the post-translational level [63]. Experiments have shown that overexpression of lncCCAT1 can reduce miR-410. Thus, an interaction between miR-410 and lncCCAT1 can be mentioned [27], [64].

Experiments showed about the role of UICLM in CRC cells, that elimination of UICLM decreased N-cadherin expression, while E-cadherin expression increased [65].

Despite its importance in colorectal cancer, little is known about tusc7. A possible mechanism for inhibiting CRC cell proliferation has been demonstrated through the sponging of miRNA-211–3p by TUSC7 in a ceRNA manner [66], [67].

Proliferation and metastasis of colorectal cancer cells are increased by FEZF1-AS1. The FEZF1-AS1 protein increased the endurance of PKM2 by binding and interacting with it, causing increased PKM2 levels cytoplasmically and nuclearly. A rise in cytoplasmic PKM2 activity lead to an increase in lactate production and pyruvate kinase activity. A further activation of STAT3 signaling was induced by FEZF1-AS1 upregulation of nuclear PKM2. The expression of FEZF1-AS1 and patient survival were significantly correlated with the expression of PKM2 in colorectal cancer tissues [68], [69].

The role of BBOX1-AS1, a newly identified long noncoding RNA, in cancer has not been studied. Cell cycle progression is enhanced by knocking down BBOX1-AS1, but apoptosis is reduced by knocking down BBOX1-AS1 [70], [71].

It appears that LINC00858 enhances cell proliferation in TP53-WT CRC cells by modulating SMAD7 via miR-25–3p regulation [72].

The current study will compare the blood expression levels of miRNAs (miR-410, miR-215, miR-211, miR-139, miR-129, miR-328, miR-197) and lncRNAs (CCAT1, UICLM, TUSC7, BBOX1, FEZF1-AS1, LINC00858, LINC00698) in both healthy and CRC Iranian patients' peripheral blood samples. Second, it will explore the correlation between the expression changes of specific miRNAs (miR-410, miR-215, miR-211, miR-139, miR-129, miR-328, miR-197) and lncRNAs (CCAT1, UICLM, TUSC7, BBOX1, FEZF1-AS1, LINC00858, LINC00698) in colorectal cancer (CRC). Finally, it will investigate the potential of the mentioned lncRNAs as Competitive Endogenous RNAs (ceRNAs) in modulating miRNA levels.