Is; c-MetCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed below the terms and conditions in the Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).1. Introduction Colorectal cancer (CRC) could be the leading cause of cancer mortality worldwide, and roughly 30 of CRC circumstances are rectal cancer [1]. Neoadjuvant chemoradiotherapy (NACRT) could be the standard treatment for individuals with locally sophisticated rectal cancerBiomedicines 2021, 9, 1371. https://doi.org/10.3390/biomedicineshttps://www.mdpi.com/journal/biomedicinesBiomedicines 2021, 9,2 of(LARC) [2,3]. Nonetheless, the response to NACRT is heterogeneous, ranging from chemoradioresistance to pathological comprehensive response (pCR). Only 150 of sufferers with LARC realize pCR PD1-PDL1-IN 1 Data Sheet following NACRT [2,4,5]. Patients with a pCR encounter superb oncological outcomes and may not require adjuvant chemotherapy [6,7]. Consequently, reputable predictive biomarkers of pCR to NACRT must be identified for personalized therapy. MicroRNAs (miRNAs), non-protein-coding RNAs, regulate the expression of their protein-coding genes by degrading mRNA or repressing translation. miRNAs contribute to numerous crucial biological functions, such as carcinogenesis, cell proliferation, and apoptosis [8,9]. They are involved in particular regulatory pathways that mediate cellular radiosensitivity. Liu et al. reported that miRNA-148b promotes radiation-induced apoptosis, thus enhancing radiosensitivity in lymphoma cells [10]. Zhend et al. indicated that radioresistance in CRC cells was induced by the acquisition of tumor-initiating cell capacity and by the overexpression of miRNA-106b, which straight targets PTEN and p21 [11]. In a single study, the overexpression of let-7a deactivated KRAS signaling and promoted radiosensitivity in lung cancer cells [12]. miRNA-148a suppresses VEGF by downregulating the pERK/HIF-1/VEGF pathway, which could inhibit angiogenesis in CRC [13]. In summary, the radiosensitivity of cancer cells is regulated by certain miRNAs; they might serve as predictors of tumor response to radiotherapy. Nonetheless, the clinical implications of these biomarkers have not been elucidated. Herein, we investigated the correlation amongst miR-148a expression and pCR in patients with LARC following NACRT and determined how miRNA-148a regulates the radiosensitivity of CRC cells. 2. Materials and Methods two.1. Sufferers and Tissue Specimens The study protocol was authorized by the Institutional Assessment Board of Kaohsiung Health-related University Hospital (KMUHIRB-02-11-2011). All participants signed an informed consent type. From May perhaps 2012 to March 2015, 51 patients with LARC treated with NACRT and radical resection had been enrolled, and pretreatment cancer tissues were collected throughout colonoscopic biopsy and used for miRNA analysis. NACRT consisted of 50 Gy of irradiation concurrently with 5-fluorouracil-based chemotherapy. Radical resection was performed 82 weeks right after NACRT. A pCR was indicated by the absence of any viable cancer cells inside the major tumor and lymph nodes. Sufferers have been dichotomized as outlined by their pathological response into pCR and non-pCR groups. The design in the identification in the candidate miRNA is shown in Figure 1A, along with the prospective regulatoryof 17 Biomedicines 2021, 9, x FOR PEER Review 3 pathway of miRNA-148a is illustrated in Figure 1B.Figure 1. The study design and hypothesis. (A) The style of identifi.
