Discovery of extracellular vesicle-delivered miR-185-5p in the plasma of patients as an indicator for advanced adenoma and colorectal cancer

Abstract

Background We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). Methods We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. Results We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. Conclusion EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).

MKLN1-AS promotes pancreatic cancer progression as a crucial downstream mediator of HIF-1α through miR-185-5p/TEAD1 pathway

“…Previous research has shown different results on the influence of miR-185-5p on cancer advancement, with contradictory functions observed as both inhibiting and promoting tumor growth (Scognamiglio et al 2022 ; Değerli et al 2020 ; Yu et al 2022 ). A recent research discovered that miR-185-5p delivered through extracellular vesicles in the blood of individuals can serve as a marker for advanced adenoma and colorectal cancer (Shi et al 2023 ). In the field of PDAC research, it has been highlighted that miR-185-5p exerts regulatory control over non-protein coding RNA, thereby fostering the progression of pancreatic cancer (Li et al 2021 ).…”

Prophylaxis with abemaciclib delays tumorigenesis in dMMR mice by altering immune responses and reducing immunosuppressive extracellular vesicle secretion

“…EVs are secreted from almost all cell types, act as mediators of intracellular communication and are considered early biomarkers of disease [ 48 ]. They may even participate in immunomodulatory oncogenic processes, reshape immune function, and are early indicators of cancer-associated thrombosis [ [49] , [50] , [51] ]. Here, we studied EVs at the experimental endpoint with a focus on immune modulation and coagulation.…”

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

“…Increasing evidence reveals that non-coding RNA overexpression or depletion accelerates CRC development and growth, representing potential molecular prognostic and therapeutic biomarkers [8]. Indeed, aberrant expression of several miR-NAs, including miR-21, miR-146b, miR-342-3p, miR-185-5p, miR-675-5p, miR-128-1-5p, miR-138-5p, and miR-451, is frequently found in CRC [9][10][11][12][13][14][15][16]. Moreover, the miR-148a-3p gene, located on the 7p15.2 region of human chromosomes, also plays a critical role in the carcinogenesis and progression of many cancer types, including CRC [17][18][19][20].…”