Silencing Lin28 promotes apoptosis in colorectal cancer cells by upregulating let‑7c targeting of antiapoptotic BCL2L1

Abstract

Colorectal cancer (CRC) remains a primary contributor to cancer-associated mortality. The Lin28/let-7 axis has previously been verified to participate in numerous pathophysiological processes involved in CRC. However, the potential roles and underlying mechanisms of this axis in apoptosis during CRC remain to be fully elucidated. The present study aimed to evaluate the role and reveal the molecular mechanisms of the Lin28/let-7 axis in the apoptosis of CRC cells. An MTT assay was conducted to assess the cell viability of HCT116 and HT29 CRC cells, and caspase-3 activity was analyzed to measure the apoptosis of CRC cells. Western blotting and reverse transcription-quantitative polymerase chain reaction were performed to examine the expression of Lin28, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, Bcl-2-like 1 (BCL2L1) and let-7c. The present study demonstrated that Lin28 was upregulated whereas let-7c was downregulated in CRC tissues and cell lines compared with normal tissues and NCM460 normal colon epithelial cells, respectively. Forced overexpression of let-7c promoted apoptosis in CRC cells, which was at least partially mediated via the targeting of BCL2L1. Furthermore, knockdown of Lin28 decreased viability and promoted apoptosis in CRC cells, whereas this effect was attenuated by let-7c inhibition. The findings of the present study suggest the involvement of the Lin28/let-7c axis in apoptosis during CRC, and indicate the potential role of this pathway as a novel therapeutic target in CRC.

PVT1 Long Non-coding RNA in Gastrointestinal Cancer

“…In line with this observation, the expression of PTV1 Sv-214 and let7a negatively correlated in colorectal cancer patient samples (Figure 5). Notably, Lin28 cooperates with Wnt signaling and Snail to drive growth and invasiveness in colorectal and gastric tumors, respectively (135)(136)(137). Conversely, in gastric cancer cell line systems, miR-128 was shown to target TrkC (79) (Figure 5).…”

Post-transcriptional Regulation of Colorectal Cancer: A Focus on RNA-Binding Proteins

“…LIN28 is an evolutionarily conserved RBP and an emerging oncogenic driver (Zhang et al, 2018). Mammals produce two LIN28 paralogs, LIN28A and LIN28B which are separately or jointly involved in various biological functions; including metabolism development, tissue regeneration, and oncogenesis (Tu et al, 2015; Wang T. et al, 2015; Jiang and Baltimore, 2016; Wang et al, 2016; Pereira et al, 2017).…”

Diverse roles of RNA‐binding proteins in cancer traits and their implications in gastrointestinal cancers

“…Elevated expression of LIN28B in CRCs cooperated with activation of Wnt signaling and increased tumor formation in carcinogen‐induced mouse model (Tu et al, ). Silencing of LIN28B in CRC cells induced apoptosis via upregulating let‐7c‐targeting of antiapoptotic BCL2L1 (H. Zhang et al, ). LIN28A was also upregulated in ~70% of CRC patients, which promoted progression of the disease (Tu et al, ; T. Wang et al, ).…”