Background: The Long noncoding RNAs (lncRNAs) have been recognized as pivotal regulators in the development of colorectal cancer (CRC). In this study, we aim to evaluate the impact of lncRNA matrilin 1 (MATN1)-Antisense RNA 1 (AS1)/micro RNA (miRNA, miR)-200c-3p/hyaluronan synthase-2 (HAS-2) axis on CRC cells and in vivo CRC model. Methods: The expression levels of LncRNA MATN1-AS1 in CRC tissues were assessed utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) platform. The expressions of LncRNA MATN1-AS1 and miR-200c-3p were validated through reverse transcription quantitative polymerase chain reaction, while HAS-2 protein and epithelial-mesenchymal transition (EMT)- related protein expressions were examined using western blot analysis. The enrichment of lncRNA MATN1-AS1 and miR-200c- 3p was evaluated using RNA Binding Protein Immunoprecipitation (RIP). The binding sites between miR-200c-3p and lncRNA MATN1-AS1 or HAS-2 were predicted by StarBase and confirmed through dual-luciferase reporter assay. Additionally, colony formation assay was performed to assess CRC cell proliferation. Transwell migration assay and invasion assay were conducted to evaluate the migratory and invasive abilities of CRC cells. An in vivo model was established by subcutaneous injection in BALB/c nude mice, while lung metastasis models were created through caudal vein injection. Immunohistochemistry was employed for the detection of HAS-2 protein in vivo. Results: The expression of LncRNA MATN1-AS1 was found to be upregulated in both CRC tissues and cells. Subsequently, dual-luciferase reporter assay was performed to demonstrate the interaction between miR-200c-3p and lncRNA MATN1-AS1, which was further confirmed by RNA immunoprecipitation (RIP) assay. Suppression of miR-200c-3p rescued low CRC cell proliferation, migratory and invasive abilities. EMT caused by the knockdown of lncRNA MATN1-AS1. HAS-2 is identified as a target that is negatively regulated by miR-200c-3p, highlighting a critical interaction within the CRC molecular landscape. As for in vivo detections, tumor weight and volume were suppressed via the downregulation of lncRNA MATN1-AS1. Additionally, lncRNA MATN1-AS1 downregulation inhibited lung metastasis and suppressed HAS-2 protein levels. Conclusion: The MATN1-AS1/miR-200c-3p/HAS-2 axis was shown to regulate CRC cell proliferation, invasiveness, migration, EMT, and tumorigenesis in vivo.

long noncoding RNA MATN1-AS1; MicroRNA-200c-3p; hyaluronan synthase 2; colorectal cancer

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