EGFR-inhibitor (Cetuximab) is one of the main targeted drugs used for metastatic colorectal carcinoma (CRC). The benefit from Cetuximab appears to be limited to a subtype of patients, not for the patients with tumors harboring mutated BRAF or KRAS genes; unfortunately, it accounts for ~40-50% of CRC cases. Previous studies have connected higher expression levels of miR-378 to be commonly presented in patients without BRAF or KRAS mutants than in mutated CRCs. The microRNA-378 (miR-378) is coexpressed with PGC-1β and can be easily induced by fatty acid, for example lauric acid. Therefore, we hypothesized that elevation of miR-378 expression in mutated CRCs may stimulate the cell response to Cetuximab. Herein, seven CRC cell lines with confirmed mutation status were involved in two parallel experiments; directly in vitro transfected miR-378 mimics, and using lauric acid to indirectly induce the level of miR-378 in cells. After the increase of miR-378 in cells by either direct or indirect approaches, sensitivity to Cetuximab was restored in all BRAF mutants (p-value <0.0001-0.0003), and half of KRAS mutants CRC (p-value 0.039-0.007). Further evidence was gained by decreasing expression of MEK and ERK2 proteins after transfection with miR-378; it was similar to the indirect induction by lauric acid approach. In conclusion, the present study demonstrated that lauric acid may efficiently induce miR-378 expression in CRC mutants, and both BRAF and a subtype of KRAS mutants presented significantly improved sensitivity to Cetuximab. Notably, BRAF mutants could even be inhibited in cell proliferation after elevated concentration of miR-378 in cells without combining with targeted therapy. This new approach may shed new light on BRAF or KRAS mutation in CRC patients for clinical trial, since lauric acid may easily be obtain from natural food, and it is supposed to be harmless to the cardiovascular system.

The screening and diagnosis of cancer are hallmarks of medicine in the aging population. Recently, microRNAs have shown potential for use as biomarkers, which could advance the field of diagnostics. The presence of miRNA-141 in the serum has been well described in several malignancies. However, the invasive approach used for sampling represents the major limitation for its practical application and, hence, its notable absence as a method for screening the general population. In light of this, we aimed to develop a high-sensitivity microRNA (miR) biosensor for application in the diagnosis of all miR-141-associated cancers, such as colorectal cancer (CRC) and breast cancer (BC). The novelty lies in our dual-probe design, which is reliant on the hybridization of the fluorescein isothiocyanate (FITC) targeting probe onto an existing sample of urinary miR-141 in the first step, followed by complementary binding with a biotinylated probe that has been coated on a modified screen-printed carbon electrode (SPCE). The hybridization of the probe and sensor produces signals via the catalytic reduction of H2O2 at HRP-modified SPCEs in the presence of H2O, which was measured by either cyclic voltammetry or chronoamperometry (CA) currents. In our study, the detection and expression of miR-141 in a cohort of colorectal cancer (n = 6) and breast cancer (n = 4) samples showed that its levels were significantly higher than in a healthy cohort (n = 9) (p < 0.004). Moreover, our miR sensor demonstrated high stability, reliability, and sensitivity (p < 0.0001). This work hopefully provides new information for the detection and monitoring of de novo and existing cancers.

It is known that colorectal cancer (CRC) cells containing mutations of the genes KRAS and BRAF are predominate mechanisms causing resistance to epidermal growth factor receptor (EGFR) inhibitors, and commonly exhibit a lower expression of microRNA-378 (miR-378) when compared with the wild type. In the present study, the aim was to determine the possible mechanism which associates miR-378 with the mitogen-activated protein kinase pathway, and to determine the efficiency of eicosapentaenoic acid ethyl ester (EPA) in its ability to restore sensitivity towards cetuximab, an EGFR inhibitor. The results demonstrated that a combined treatment of 40 µM EPA with 0.2 µM cetuximab can significantly suppress the cell growth in KRAS-mutant and control wild-type cells. Furthermore, the higher phosphorylated protein level of extracellular-signal-regulated kinase 1/2 was notable in KRAS EPA-treated cells (P=0.006-0.047) and resulted in significantly increased cell death; however, inconsistent results were indicated in EPA-treated BRAF-mutant cells, compared with the original cells (without treatment). KRAS-mutant and wild-type Caco-2 cells treated with EPA exhibited increased cetuximab response rates, but these response rates were reduced in the BRAF-mutant cells. In conclusion, upregulation of miR-378 induced by EPA may result in the significant restoration of sensitivity to cetuximab in the KRAS-mutant cells. The present data will contribute to a notable potential therapeutic solution for future clinical CRC treatments.

Due to the severe acute respiratory syndrome coronavirus (SARS-CoV-2, also called coronavirus disease 2019 (COVID-19)) pandemic starting in early 2020, all social activities ceased in order to combat its high transmission rate. Since vaccination combats one aspect for halting the spread of the virus, the biosensor community has looked at another aspect of reducing the burden of the COVID-19 pandemic on society by developing biosensors that incorporate point-of-care (POC) testing and the rapid identification of those affected in order to deploy appropriate measures. In this study, we aim first to propose a screen-printed carbon electrode (SPCE)-based electrochemical biosensor that meets the ASSURED criteria (i.e., affordable, sensitive, specific, user-friendly, rapid, equipment-free, and deliverable) for POC testing, but more importantly, we describe the novelty of our biosensor’s modifiability that uses custom dual probes made from target nucleic acid sequences. Additionally, regarding the sensitivity of the biosensor, the lowest sample concentration was 10 pM (p = 0.0257) without amplification, which might challenge the traditional technique of reverse transcriptase-polymerase chain reaction (RT-PCR). The purpose of this study is to develop a means of diagnostics for the current pandemic as well as to provide an established POC platform for future epidemics.

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