LINC01116 facilitates colorectal cancer cell proliferation and angiogenesis through targeting EZH2-regulated TPM1

Weijie Liang,Xinguang Qiu,Jie Wu

doi:10.1186/s12967-021-02707-7

LINC01116 facilitates colorectal cancer cell proliferation and angiogenesis through targeting EZH2-regulated TPM1

Weijie Liang, Xinguang Qiu + Show 1 more

Open Access

https://doi.org/10.1186/s12967-021-02707-7

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Abstract

BackgroundColorectal cancer (CRC) is a common malignant tumor globally. Meanwhile, LINC01116 has been proposed as risk factor for various tumors, including CRC. But the regulation of LINC01116 in CRC required more validated data. This study aimed to elucidate the potential function of LINC01116 in regulating cell proliferation and angiogenesis of CRC.MethodsLINC01116 expression in 80 pairs of CRC tumor and adjacent non-tumor tissues was determined by qRT-PCR. After transfection of pcDNA3.1-LINC01116, sh-LINC01116, sh-TPM1, pcDNA3.1-EZH2 or sh-EZH2 in SW480 and HCT116 cells, the levels of LINC01116, TPM1 and EZH2 were measured by qRT-PCR or Western blot. The cell biological function of CRC cell lines was determined by CCK-8, colony formation assays, tube formation and scratch assays. RNA pull-down and RIP assays were applied to detect the binding of LINC01116 with EZH2 and H3K27me3. Binding of EZH2 to the TPM1 promoter was assessed by ChIP assay. Finally, xenograft models in nude mice were established to validate the results of in vitro experiments.ResultsLINC01116 was overexpressed in CRC tissues and high expression of LINC01116 was negatively correlated with postoperative survival. In vitro study showed LINC01116 expression could significantly enhance CRC progression, including increasing cell proliferation, migration and angiogenesis. Besides, investigations into the mechanism disclosed that LINC01116 could regulate EZH2 to inactivate TPM1 promoter, thus promoting CRC cell proliferation and angiogenesis. Moreover, consistent results of in vivo experiments were conformed in vitro experiments.ConclusionLINC01116 promotes the proliferation and angiogenesis of CRC cells by recruiting EZH2 to potentiate methylation in the TPM1 promoter region to inhibit the transcription of TPM1.

Highlights

Colorectal cancer (CRC) is a common malignant tumor globally
LINC01116 is highly expressed in CRC tissues To determine whether LINC01116 was dysregulated in CRC, qRT-PCR was applied to measure LINC01116 expression in 80 pairs of CRC tumor and adjacent normal tissues
The results showed that SW480 and HCT116 cell proliferation activity and number of clones of sh-LINC01116 + sh-tropomyosin 1 (TPM1) group were increased compared with sh-LINC01116 group (Fig. 3h, i, P < 0.05). sh-LINC01116 + sh-TPM1 group had elevated cell migration ability and total tube length than sh-LINC01116 group (Fig. 3j,k, P < 0.05)

Summary

Introduction

Colorectal cancer (CRC) is a common malignant tumor globally. This study aimed to elucidate the potential function of LINC01116 in regulating cell proliferation and angiogenesis of CRC. As one of the most common malignancies worldwide, colorectal cancer (CRC) accounts for nearly 8.5% of the total cancer-related deaths [1]. Tumor angiogenesis is crucial for sustained cell metastasis and tumor proliferation [4]. Suppression of tumor angiogenesis is one of the important strategies to hinder tumor metastasis and growth. Traditional anti-angiogensic therapies sometimes induced hypoxia and metastasis which might speed up the growth of tumor cells [5, 6]. To maximize the efficiency of anti-angiogensic therapies in CRC, identification of modulatory mechanisms that regulate angiogenesis is essential for CRC treatment.

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