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 decreased survival in CRC and urogenital cancer [22,23]. In line with earlier ciated with decreased survival in CRC and urogenital cancer [22,23]. In line with earlier studies, we observed that miRNA-148a overexpression was associated having a pCR folstudies, we observed that miRNA148a overexpression was related having a pCR follow lowing NACRT and enhanced survival in patients 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 N-Hexanoyl-L-homoserine lactone Data Sheet development and strated that overexpressed miRNA148a in CRC cells inhibited cell development and induced induced apoptosis in vitro, also as inhibiting tumor growth in vivo, even in the absence apoptosis in vitro, as well as inhibiting tumor growth in vivo, even inside 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 utilizing two CRC cell lines with distinct mutational statuses [24]. HT29 cells are more radioresistant, whereas HCT116 cells are additional radiosensitive [25,26]. Herein, the radio-sensitization of miRNA148a was more prominent in the HT29 cells than in the HCT116 cells. Moreover, radiation induced the upregulation of c-Met within the HCT116 cells, but not in the HT29 cells. This may well be attributable towards the differences in their mutational statuses. Bacco et al. demonstrated that the irradiation-induced expression of c-Met was related to the activation of ATM and NF-kB [27]. Lin et al. analyzed 167 CRC specimens, detecting an association among NF-B activation and KRAS mutation [28]. KRAS is really a mutation in HCT116 cells but is WT in HT29 cells [24]; therefore, we speculated that irradiation-induced c-Met upregulation was prominent within the HCT116 cells and not the HT29 cells due to the fact NF-B activation may be related to 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 Maresin 1 web response to irradiation in vivo [30]. Within 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 popular in gastrointestinal cancer and is deemed to be associated with tumor progression and poor survival. c-Met is a receptor tyrosine kinase that binds to hepatocyte growth aspect and triggers many cancer-associated processes, such as proliferation, angiogenesis, invasion, and epithelial esenchymal transition [31]. c-Met overexpression in sufferers with CRC has been associat.