MiR-378a-3p Acts as a Tumor Suppressor in Colorectal Cancer Stem-Like Cells and Affects the Expression of MALAT1 and NEAT1 lncRNAs

Abstract

MiR-378a-3p plays a critical role in carcinogenesis acting as a tumor suppressor, promoting apoptosis and cell cycle arrest and reducing invasion and drug resistance in several human cancers, including colorectal cancer (CRC), where its expression is significantly associated with histological classification and prognosis. In this study, we investigated the biological and cellular processes affected by miR-378a-3p in the context of CRC carcinogenesis. In agreement with the literature, miR-378a-3p is downregulated in our cohort of CRC patients as well as, in 15 patient-derived colorectal cancer stem-like cell (CRC-SC) lines and 8 CRC cell lines, compared to normal mucosae. Restoration of miR-378a-3p restrains tumorigenic properties of CRC and CRC-SC lines, as well as, significantly reduces tumor growth in two CRC-SC xenograft mouse models. We reported that miR-378a-3p modulates the expression of the lncRNAs MALAT1 and NEAT1. Their expression is inversely correlated with that of miR-378a-3p in patient-derived CRC-SC lines. Silencing of miR-378a-3p targets, MALAT1 and NEAT1, significantly impairs tumorigenic properties of CRC-SCs, supporting the critical role of miR-378a-3p in CRC carcinogenesis as a tumor-suppressor factor by establishing a finely tuned crosstalk with lncRNAs MALAT1 and NEAT1.

LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer

“…GAPDH was used as the control. MALAT1: FW: GGA TCC TAG ACC AGC ATG CC; RV: AAA GGT TAC CAT AAG TAA GTT CCA GAA AA ( 31 ). The detailed method for PCR was described previously ( 32 ).…”

Novel biomarkers for neoplastic progression from ulcerative colitis to colorectal cancer: a systems biology approach

“…in the other word, the centrality of the network (hub genes), and interactions with them form an essential part of the analysis path. Also, in some recent studies, the important role of miR-378a-5p in the initiation and progression of cancer or UC disease has been pointed out through different mechanisms 27 – 30 . Accordingly, we have focused on the importance, novelty, and ability to directly target hub genes (DEGs) in the regulatory network of UC progression to CRC carcinogenesis, on network centrality and a higher degree of connectivity among nodes rather than miRNA.…”

Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance

“…In the setting of CRC carcinogenesis, Castellani et al studied the biological and cellular processes impacted by miR-378a-3p [ 88 ]. They investigated its interactions with two lncRNAs—MALAT-1 and Nuclear Paraspeckle Assembly Transcript 1 (NEAT1)—to better understand its effects on CRC-SCs (CRC stem-like cells) [ 88 ]. MALAT-1 and NEAT1, markedly excessively expressed in various kinds of cancer, have been shown to be promoters of multiple biological processes.…”

“…It was determined that the expression of miR-378a-3p was reinstated, resulting in a reduction of tumorigenicity in both CRC and CRC stem cell (CRC-SC) lines. Furthermore, miR-378a-3p restoration dramatically reduced tumor development in two CRC-SC xenograft animal models, indicating tumor-suppressive activity in CRC [ 88 ]. The study demonstrates that the expression of two lncRNAs, MALAT-1 and NEAT1, is regulated by miR-378a-3p [ 88 ].…”

“…Furthermore, miR-378a-3p restoration dramatically reduced tumor development in two CRC-SC xenograft animal models, indicating tumor-suppressive activity in CRC [ 88 ]. The study demonstrates that the expression of two lncRNAs, MALAT-1 and NEAT1, is regulated by miR-378a-3p [ 88 ]. MALAT-1 and NEAT1 expressions were shown to be inversely related to miR-378a-3p in patient-derived CRC-SC lines.…”