LncRNA MIAT Promotes the Proliferation and Invasion of Colorectal Cancer via Suppressing Apoptosis and Senescence

Background: Myocardial infarction-associated transcript (MIAT) is a long noncoding RNA (lncRNA), which functions in a variety of disorders, like myocardial infarction and diabetic retinopathy. Moreover, recent reports have established that MIAT is upregulated in several types of malignancies and plays a crucial role in tumorigenesis. Therefore, this research aimed to investigate the expression of MIAT in colorectal cancer (CRC) and further evaluate the impact of its knocking-down on the proliferation and migration of the CRC cell.Method: In this case-control experimental study, we evaluated the expression level of MIAT in a series of CRC and marginal tissues using RT-qPCR. Furthermore, the role of MIAT was assessed employing RNA interference (RNAi)-mediated suppressing strategy in CRC-derived cells. Subsequently, colony formation, cell cycle analysis, migration, apoptosis, and senescence assays were done to decipher the influence of MIAT on initiation and progression of CRC.Results: Our findings revealed that MIAT expression is significantly upregulated in high-grade and vascular invasion tumor tissues. Furthermore, MIAT silencing led to G۱ arrest in SW۱۱۶ and SW۴۸ CRC-derived cells. We also found that MIAT inhibition contributed to the induction of apoptosis/cellular senescence as well as the limitation of colony formation capability and cell migration in CRC cells. The obtained findings also showed that MIAT silencing dysregulated the expression of ATM and CHK۲ genes known as DNA damage responsive genes.Conclusion: The results of the present study demonstrated that lncRNA MIAT may control CRC cell proliferation and metastasis through regulating DNA damageresponsive pathway and can be noticed as a potential marker for diagnosis, prognosis, and targeted-therapy of high-grade CRC.

کلیدواژه ها:

MIAT long non-coding RNA ، Colorectal neoplasms ، Cellular senescence ، DNA Damage