4.7 Article

CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 interaction: In-silico and clinically implicated in CRC progression, correlated to tumor stage and size in case-controlled study; step toward ncRNA precision

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DOI: 10.1016/j.ijbiomac.2023.126739

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Colorectal cancer; lncRNA CCDC144NL-AS1; Hsa-miR-143-3p; HMGA2; Liquid biopsy; In silico analysis

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This study unraveled the regulatory mechanism of lncRNA CCDC144NL-AS1 in colorectal cancer (CRC) and its interaction with hsa-miR-143-3p and HMGA2. The results showed that CCDC144NL-AS1 expression was upregulated in CRC patients, while hsa-miR-143-3p and HMGA2 expression were downregulated. There were significant correlations between CCDC144NL-AS1 and HMGA2, as well as between lncRNA CCDC144NL-AS1 and hsa-miR-143-3p. These findings suggest that the CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 interaction arm may play a role in CRC progression.
Unravel the regulatory mechanism of lncRNA CCDC144NL-AS1 in CRC hsa-miR-143-3p, downstream protein HMGA2 interaction arm, association with clinicopathological characteristics. Using peripheral blood as liquid biopsy from 60 CRC patients and 30 controls. The expression levels of CCDC144NL-AS1 and hsa-miR-143-3p detected by qRT-PCR. CCDC144NL-AS1 expression was significantly upregulated in CRC patients' sera, associated with worse CRC clinicopathological features regarding the depth of tumor invasion and highly significant difference between tumor stages 3 and 4 and tumor stages 2 and 4. While, hsa-miR-143-3p expression was downregulated in CRC patients by 4.5-fold change when compared to the control subjects (p < 0.0001) and HMGA2 increased in CRC patients than controls 19.59 ng/mu L and 5.377 ng/mu L, respectively (p < 0.0001) with significant difference between tumor stages 3 and 4 as well as tumor stages 2 and 4. CRC patients with large tumor size showed upregulation in CCDC144NL-AS1 expression and HMGA2 levels compared to those with small tumor size (p-value = 0.0365 and 0.013, respectively). CCDC144NL-AS1 and HMGA2 were positively correlated, whereas lncRNA CCDC144NL-AS1 and hsa-miR-143-3p were negatively correlated. Conclusion: As an interaction arm CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 were correlated to CRC stages 2-4. Therefore, this interaction arm expression clinically and in silico approved, would direct treatment precision in the near future.

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