Colorectal Cancer Migration and Invasion Initiated by microRNA-106a

Abstract

MicroRNAs have been implicated in the regulation of several cellular signaling pathways of colorectal cancer (CRC) cells. Although emerging evidence proves that microRNA (miR)-106a is expressed highly in primary tumor and stool samples of CRC patients; whether or not miR-106a mediates cancer metastasis is unknown. We show here that miR-106a is highly expressed in metastatic CRC cells, and regulates cancer cell migration and invasion positively in vitro and in vivo. These phenotypes do not involve confounding influences on cancer cell proliferation. MiR-106a inhibits the expression of transforming growth factor-β receptor 2 (TGFBR2), leading to increased CRC cell migration and invasion. Importantly, miR-106a expression levels in primary CRCs are correlated with clinical cancer progression. These observations indicate that miR-106a inhibits the anti-metastatic target directly and results in CRC cell migration and invasion.

Cellular Localization, Invasion, and Turnover Are Differently Influenced by Healthy and Tumor-Derived Extracellular Matrix

“…On the contrary, these cells spread in the perilesional-and CRCderived ECM over time. These findings are in agreement with previous reports indicating an invasive phenotype of these cells in Matrigel 44 and xenograft models. 34,46 Our findings highlight a relevant role of the healthy ECM in constraining the spread of tumor cells with invasive capacity, as LoVo and SW480 cells.…”

“…43 HT29 cells have been reported to have modest invasive capacity in Matrigel. 44 In vivo, depending on the xenograft model HT29 cells have been reported to remain confined in the tumor mass 44 or invade the surrounding tissue. 44,45 All these findings indicate that the ability of HT29 cells to spread out from the primary site depend on the microenvironment in which they were seeded.…”

“…44 In vivo, depending on the xenograft model HT29 cells have been reported to remain confined in the tumor mass 44 or invade the surrounding tissue. 44,45 All these findings indicate that the ability of HT29 cells to spread out from the primary site depend on the microenvironment in which they were seeded. SW480 (CRC grade III) and LoVo cells (CRC grade IV) were found in the crypts and stroma of healthy-derived ECM, and over time few cells remained in the stroma.…”

mir‑106a regulates cell proliferation and apoptosis of colon cancer cells through targeting the PTEN/PI3K/AKT signaling pathway

“…2), which was in consistent with previous studies that reported high expression of miR-106a in cancer tissues of CRC patients (17,18); meanwhile, compared to NCM640 cells, miR-106a was significantly elevated in SW620 and HT29 cell lines (Fig. 3), which was in line with a previous study (19). These results together suggested the oncogenetic role of miR-106a in CRC patients and in SW620/HT29 cells.…”

Regulation of miR106b cluster through the RB pathway

“…[14][15][16] For example, deregulated miRNA expression has been implicated in aberrant proliferation, genome stability and epithelial-mesenchymal transition. [17][18][19] Analyses of miRNA expression in breast cancer tumor specimens have demonstrated association with specific breast cancer subtypes. Additionally, specific miRNA species are correlated with specific facets of breast cancer biology and prognosis.…”