Long Non-Coding RNA HAND2 Antisense RNA 1 Inhibits Colorectal Cancer Development by Sponging microRNA-3118/Leptin Receptor Axis.

This study aimed to examine the function of long non-coding RNA HAND2 antisense RNA 1 (HAND2-AS1) in colorectal cancer (CRC) and explore its underlying mechanism of action. HAND2-AS1, microRNA (miR)-3118, and leptin receptor (LEPR) levels were determined using western blot analysis and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RNA-binding protein immunoprecipitation (RIP) and luciferase reporter assays were performed to evaluate the relationship between HAND2-AS1, miR-3118, and LEPR. Overexpression of genes in CRC cell lines was performed by transfection with the overexpression vector or miR-mimic. Cell proliferation, migration, and apoptosis-related protein levels were evaluated using the Cell Counting Kit-8 (CCK-8), Transwell, and western blotting assays. A CRC xenograft mouse model was established to verify the role of HAND2-AS1 in CRC in vivo. In both CRC cell lines and CRC tumor samples the HAND2-AS1 expression was reduced. Upregulation of HAND2-AS1 levels inhibited CRC cell line proliferation and migration, initiated apoptosis, and suppressed the growth of CRC xenografted tumors. In addition, HAND2-AS1 sponges miR-3118, which is up-regulated in CRC. Moreover, miR-3118 overexpression promoted CRC cell line proliferation along with cell migration, but hindered apoptosis of cells, along with altering the consequences of high expression levels of HAND2-AS1 in CRC cells. In addition, miR-3118 can target LEPR, which is downregulated in CRC. The effect of miR-3118 on CRC cells was blocked by LERP overexpression. HAND2-AS1 effectively inhibited CRC progression by sponging the miR-3118-LEPR axis. Our results may facilitate the development of therapeutic interventions for CRC.

Yi C ，Zhao C ，Peng C 《-》

LncRNA HAND2-AS1 inhibits 5-fluorouracil resistance by modulating miR-20a/PDCD4 axis in colorectal cancer.

Chemoresistance is one of the main obstacles in the therapy of human cancers, including colorectal cancer (CRC). Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) has been demonstrated to be associated with CRC. However, the function of HAND2-AS1 in 5-Fluorouracil (5-FU) resistance of CRC remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HAND2-AS1, miR-20a and programmed cell death factor 4 (PDCD4) mRNA. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate IC50 of 5-FU and cell proliferation. Flow cytometry analysis was used to determine cell apoptosis. Transwell assay was carried out to measure cell migration and invasion. Western blot assay was conducted to examine the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), matrix metalloprotein 2 (MMP2), MMP9 and PDCD4. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were utilized to verify the combination between miR-20a and HAND2-AS1. Dual-luciferase reporter assay was used to analyze the association between miR-20a and PDCD4. Murine xenograft assay was used to confirm the function of HAND2-AS1 in vivo. HAND2-AS1 and PDCD4 were downregulated and miR-20a was upregulated in 5-FU-resistant CRC tissues and cells. HAND2-AS1 suppressed 5-FU resistance, cell proliferation, migration and invasion and promoted cell apoptosis in 5-FU-resistant CRC cells. HAND2-AS1 acted as a sponge of miR-20a to regulate PDCD4 expression. Moreover, HAND2-AS1 suppressed cell progression and 5-FU resistance by upregulating PDCD4 via sponging miR-20a in 5-FU-resistant CRC cells. Besides, HAND2-AS1 inhibited tumor growth in vivo. HAND2-AS1/miR-20a/PDCD4 axis inhibited cell progression and 5-FU resistance in 5-FU-resistant CRC cells.

Jiang Z ，Li L ，Hou Z ，Liu W ，Wang H ，Zhou T ，Li Y ，Chen S ... -  《-》

Upregulated lncRNA Cyclin-dependent kinase inhibitor 2B antisense RNA 1 induces the proliferation and migration of colorectal cancer by miR-378b/CAPRIN2 axis.

Zheng Y ，Zeng J ，Xia H ，Wang X ，Chen H ，Huang L ，Zeng C ... -  《-》

Long non-coding RNA TP73-AS1 sponges miR-194 to promote colorectal cancer cell proliferation, migration and invasion via up-regulating TGFα.

Cai Y ，Yan P ，Zhang G ，Yang W ，Wang H ，Cheng X ... -  《-》

LncRNA TTN-AS1 sponges miR-376a-3p to promote colorectal cancer progression via upregulating KLF15.

Long non-coding RNAs (lncRNAs) play key roles in regulating multiple cancers. TTN-AS1 was reported to function in several human malignancies. However, the biological function of TTN-AS1 in colorectal cancer (CRC) has not been explored. In this study, we aimed to investigate the role and the underlying mechanisms of TTN-AS1 in CRC progression. RT-qPCR was used to detect the expression levels of TTN-AS1, miR-376a-3p and KLF15 in colorectal cancer tissues and cells. CCK-8, colony formation, flow cytometry and transwell assays were performed to determine the cell proliferation, apoptotic rate and invasion ability. Target genes were predicted using bioinformatics methods. si-RNA and miRNA inhibitor were transfected into CRC cells to explore the underlying mechanisms. Tumor xenografts were created to confirm the function of TTN-AS-1 in vivo. TTN-AS1 upregulation was observed both in CRC tissues and cell lines. Functional investigation showed that knockdown of TTN-AS1 inhibited CRC cell proliferation and invasion, while enhanced cell apoptosis. Bioinformatics analysis identified miR-376a-3p as a target of TTN-AS1. Transfection of miR-376a-3p inhibitor mitigated the alterations induced by TTN-AS1 knockdown. Moreover, TTN-AS1 positively regulated KLF15 via sponging miR-376a-3p. Additionally, these findings were supported by in vivo experiments. In conclusions, TTN-AS1 promoted CRC proliferation and invasion through miR-376a-3p/KLF15 axis. Our findings suggested that TTN-AS1 might be a potential therapeutic target in CRC treatment.

Wang Y ，Jiang F ，Xiong Y ，Cheng X ，Qiu Z ，Song R ... -  《-》