## 4 Discussion  
### Overview of Meta-Analyses and microRNA in CRC  
Small, non-coding RNA segments known as microRNAs (miRNAs) are essential for controlling the expression of certain genes. Their length ranges from 18 to 25 nucleotides, and they play a role in post-transcriptional control by attaching to messenger RNAs  
Figure 8: Funnel plot of overall miRNA for diagnosis CRC. The symmetrical distribution of studies suggests that there is little publication bias in the studies that were included in the research.  
(mRNAs) and causing translation inhibition or mRNA destruction [9; 26]. Numerous cellular functions, including differentiation, development, and reaction to environmental changes, depend on this regulatory role. Since their discovery in 1993, miRNAs have been identified as essential participants in numerous illnesses' etiology, including cancer [27; 28]. MiRNA failure and ectopic expression are known to be linked with cancer through a deletion in the gene fragile sites, and this condition might be associated with miRNA genes' hereditary or acquired mutations or miRNA promoters' methylation [29].  
MiRNAs are essential to epigenetic processes in addition to being involved in the control of gene expression. Target gene expression can be impacted by their ability to modify DNA methylation patterns and chromatin structure [30]. In the cancer setting, abnormal miRNA expression shows the oncogenes activation or the silence of tumor suppressor genes, therefore, epigenetic regulation is crucial. For example, it has been demonstrated that miRNA-21 overexpressed colorectal cancer tissues and targets multiple tumor suppressor genes, which aids in the advancement of cancer [27].  
The favorable biomarkers in the early diagnosis and detection of several malignancies, including colorectal cancer, have emerged: miRNA. Their capacity to determine the biomarker fluctuates for each type of miRNA, as seen in Table 3. According to this study, five miRNAs had a high sensitivity (>90%), which are miRNA-19a (91%), miRNA-139-3p (96.6%), miRNA-21 (91.4%), miRNA-320a (92.8%), and miRNA (423-5p). The highest sensitivity and specificity are found in miRNA-139-3p (96.6% and 97.8%). miRNA-139-3p has the highest accuracy for diagnosing colorectal cancer in the adult population. Maintaining stability in bodily fluids like blood, feces, and urine makes it perfect for non-invasive screening techniques. Certain miRNAs that are expressed differently in colorectal cancer tissues than in normal cells have been found through studies. Serum miRNA-21, which represents the tumor burden in the colon, is a reliable biomarker for colorectal cancer patients' early identification and prognosis [27; 30]. Furthermore, it has been demonstrated that fecal miRNAs, such as miRNA-29a and miRNA-224, are non-invasive biomarkers for colorectal cancer, providing a possibility for early identification and surveillance [26; 30].  
The information supplied shows the findings of research examining the odds ratios (OR) connected to colorectal cancer (CRC) and the delivery of various miRNAs. A significantly significant OR of 1.84 using a tight confidence interval (CI) (1.48-2.19, \(p<0.0001\)) is shown by analysis of the sensitivity administration of total miRNA, suggesting that the link is certain. Also, note a substantial OR of 1.43 with a narrow confidence interval (1.01-1.85, \(p<0.0001\)) on the side. The DOR assessment yields an OR of 0.38 with a broader confidence interval (\(-0.12\)-0.88), suggesting that the link is unclear. The consistency and dependability of the results are supported by the funnel plots' lack of heterogeneity and publication bias. The result highlights genetic variables in clinical risk assessment and the high diagnostic accuracy of colorectal cancer using multiple types of miRNAs. To confirm and expand on these results, more study is necessary, which could lead to better strategies for cancer prevention and treatment [8; 9; 13].