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

Abstract

Background Colorectal 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. Methods LINC01116 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. Results LINC01116 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. Conclusion LINC01116 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.

LINC01116 Promotes Migration and Invasion of Oral Squamous Cell Carcinoma by Acting as a Competed Endogenous RNA in Regulation of MMP1 Expression

“…Long intergenic noncoding RNA01116 (LINC01116) is a novel LncRNA located in the 2q31.1 region [11,12]. LINC01116 has been reported to participate in cell proliferation and invasion, cycle arrest, epithelial mesenchymal transition, and chemoresistance, and impose promotive effects on various cancers, including lung cancer [13], breast cancer [14], colorectal cancer [15], and gastric cancer [16]. Notably, LINC01116 was found to be upregulated in HNSCC, and LINC01116 knockdown could alleviate the malignancy of HNSCC cells via the epithelial mesenchymal transition pathway [17].…”

Downregulation of cell division cycle-associated protein 7 (CDCA7) suppresses cell proliferation, arrests cell cycle of ovarian cancer, and restrains angiogenesis by modulating enhancer of zeste homolog 2 (EZH2) expression

“…As an important component of polycomb group proteins (PcGs), EZH2 has been confirmed to be overexpressed in a variety of cancer types with lethal outcomes, including OC cases [ 13 , 14 ]. The EZH2 gene mainly contributes to tumor development by promoting angiogenesis, silencing tumor suppressor genes and inhibiting the apoptosis of tumor cells [ 22 , 23 ].…”

“…Moreover, EZH2 is responsible for trimethylation of histone H3 on Lys27 (H3K27me3) that results in epigenetic gene silencing. Recent research indicates that EZH2 is overexpressed in various tumor tissues and closely related to tumor infiltration, metastasis and prognosis [ 13 , 14 ]. Accordingly, inhibition of EZH2 might be a promising strategy for therapies of cancers in the future.…”

Promising Advances in LINC01116 Related to Cancer

“…Emerging evidence showed that a large number of patients were commonly diagnosed at terminal stages with high expression of LINC01116. Liang et al (2021) identified that LINC01116 facilitated the growth of CRC cells and tumorigenicity through the downregulation of TPM1 expression. Specifically, LINC01116 can bind with EZH2 to accelerate the methylation of TPM1, which blocks the transcription of TPM1.…”