Functional Effects of let-7g Expression in Colon Cancer Metastasis

Abstract

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment.

Role of epigallocatechin-3- gallate in the regulation of known and novel microRNAs in breast carcinoma cells

“…Apart from miR-21, the miR-17-92 cluster is also a known oncogenic miRNA which often up-expressed in breast ( Moi et al, 2019 ), lung ( Zhang X. et al, 2018 ), lymphomas ( Fassina et al, 2012 ), colon ( Tsuchida et al, 2011 ), liver ( Gong et al, 2018 ) cancer, etc. On the contrary, let-7 and miR-34 family are known tumor suppressor miRNAs that regulate breast ( Liu et al, 2015 ; Imani et al, 2018 ), lung ( Takamizawa et al, 2004 ; Sun et al, 2021 ), colon ( Roy et al, 2012 ; Chang et al, 2019 ), liver ( Jin et al, 2016 ; Zhang H.-F. et al, 2018 ), prostate ( Nadiminty et al, 2012 ; Hagman et al, 2013 ), ovarian ( Li et al, 2015 ; Biamonte et al, 2019 ) cancer, etc. Apart from these, altered expressions of different miRNAs are found in different cancers.…”

Small Nucleolar Derived RNAs as Regulators of Human Cancer

“…One example from this includes an early publication from 2008 by Kumar et al where let-7g was found to suppress the NSCLC phenotype both in vitro and in vivo through the RAS pathway [ 34 ]. Many publications implicating sd/let-7g as a tumor-suppressing RNA in cancer have emerged since the aforementioned review, including a 2019 publication by Chang et al in colorectal cancer and a 2019 paper by Biamonte et al in ovarian cancer [ 35 , 36 ].…”

“…miR31 is also located within a C/D Box snoRNA-like transcript (GRCh38: chr 9:21512102-21512221:-1) known to bind fibrillarin [ 28 , 29 , 30 , 31 , 32 , 33 ]. ( E ) miR-let7g (ENSG00000199150) has been shown to be downregulated in NSCLC, colorectal and ovarian cancers and is also embedded within a C/D Box snoRNA-like transcript (GRCh38: chr 3:52268239-52268408:-1) known to bind fibrillarin [ 34 , 35 , 36 ]. ( F ) miR-28 (ENSG00000207651) has been shown to be downregulated in B-cell lymphoma, prostate and breast cancer and is located within a C/D Box snoRNA-like transcript (GRCh38: chr 3:188688746-188688887:1) known to bind fibrillarin [ 37 , 38 , 39 ].…”

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

“…The lethal-7 ( let-7 ) gene was identified as the first human miRNA and functions as a key regulator in development and cancer [ 120 ]. Among 13 types of miRNAs in the let7 family, let-7g is highly associated with cancer development, including CRC [ 121 , 122 , 123 ]. One study observed a significant increase in the let-7g level in the tumor tissues of patients with CRC and its association with poor chemoresponse and disease progression in CRC [ 121 ].…”