Sis [9]. Studies have noted miRNA148a downregulation in gastrointestinal, breast, urogenital, and non-small-cell lung cancer. Notably, this downregulation has been assourogenital, and nonsmallcell lung cancer. Notably, this downregulation has been asso ciated with reduced survival in CRC and urogenital cancer [22,23]. In line with prior ciated with reduced survival in CRC and urogenital cancer [22,23]. In line with prior studies, we observed that miRNA-148a overexpression was connected with a pCR folstudies, we observed that miRNA148a overexpression was linked using a pCR adhere to lowing NACRT and improved survival in individuals with LARC. Furthermore, our study ing NACRT and improved survival in individuals with LARC. Moreover, our study demon demonstrated that overexpressed miRNA-148a in CRC cells inhibited cell growth and strated that overexpressed miRNA148a in CRC cells inhibited cell growth and Actarit Biological Activity induced induced apoptosis in vitro, as well as inhibiting tumor growth in vivo, even within the absence apoptosis in vitro, at the same time as inhibiting tumor growth in vivo, even within the absence of radi ation. This supports the premise that miRNA148a acts as a tumor suppressor miRNA.Biomedicines 2021, 9,12 ofof radiation. This supports the premise that miRNA-148a acts as a tumor suppressor miRNA. To investigate irrespective of whether miRNA-148a functioned regularly in cells bearing distinct gene mutations, we examined the biological functions of miRNA-148a by using two CRC cell lines with distinct mutational statuses [24]. HT29 cells are a lot more radioresistant, whereas HCT116 cells are far more radiosensitive [25,26]. Herein, the radio-sensitization of miRNA148a was a lot more prominent within the HT29 cells than in the HCT116 cells. In addition, radiation induced the upregulation of c-Met within the HCT116 cells, but not inside the HT29 cells. This may possibly be attributable for the variations in their mutational statuses. Bacco et al. demonstrated that the irradiation-induced expression of c-Met was associated with the activation of ATM and NF-kB [27]. Lin et al. analyzed 167 CRC specimens, detecting an association between NF-B activation and KRAS mutation [28]. KRAS is actually a mutation in HCT116 cells but is WT in HT29 cells [24]; as a result, we speculated that irradiation-induced c-Met upregulation was prominent inside the HCT116 cells and not the HT29 cells for the reason that NF-B activation might be associated with KRAS mutation. The role of miRNA-148a inside the regulation of radiosensitivity has rarely been investigated. Wang et al. identified that SNHG12, a class of extended noncoding RNAs, mediated the radiosensitivity of cervical cancer cells through the miRNA-148a/CDK1 pathway [29]. Lopez-Bertoni et al. observed that the codelivery of miRNA-148a and miRNA-296-5p inhibited the stemness of glioblastoma cells in vitro and enhanced tumor response to irradiation in vivo [30]. In this study, we observed that upregulation of miRNA-148a sensitized CRC cells to irradiation in vitro and in vivo, supporting our postulation that miRNA-148a was associated with pCR (provided that it functioned as a radiosensitizer in CRC cells). Aberrantly regulated c-Met is widespread in gastrointestinal cancer and is regarded to become connected with tumor progression and poor survival. c-Met is actually a receptor tyrosine kinase that binds to hepatocyte growth aspect and triggers many Fexinidazole custom synthesis cancer-associated processes, which includes proliferation, angiogenesis, invasion, and epithelial esenchymal transition [31]. c-Met overexpression in patients with CRC has been associat.