Abstract
Reportedly, long-chain non-coding RNA LINC00963 features prominently in cancer biology. However, functional details of LINC00963 in colorectal cancer (CRC) remain to be elucidated. Reverse transcription-quantitative (RT-q)PCR was performed to examine LINC00963 and microRNA (miR)-1281 expression levels in 53 matched pairs of cancerous and non-cancerous tissues from patients with CRC. Tripartite motif-containing 65 (TRIM65) protein expression in CRC cells was detected via western blot analysis. Furthermore, LINC00963 overexpression plasmid, LINC00963 small interfering RNA, miR-1281 mimics or miR-1281 inhibitors were transfected into CRC cells, and Cell Counting Kit-8, colony formation and Transwell assays were adopted to study the effects of LINC00963 and miR-1281 on the malignant phenotypes of CRC cells. Bioinformatics analysis, dual-luciferase, RNA pull-down and immunoprecipitation assays, RT-qPCR and western blot analysis were performed to investigate the regulatory relationship between LINC00963, miR-1281 and TRIM65. LINC00963 was highly expressed in CRC tissues and cells, while miR-1281 was downregulated. Functionally, LINC00963 facilitated the proliferation, colony formation, migration and invasion of CRC cells, and increased the expression levels of Ki67, matrix metalloproteinase (MMP)2 and MMP9, while miR-1281 had the opposite biological functions. Mechanistically, LINC00963 sponged miR-1281 and repressed its expression in CRC cells, resulting in the upregulation of TRIM65. LINC00963 positively regulates TRIM65 in CRC progression by repressing miR-1281 expression, showing potential as a therapeutic target for treating CRC.
Highlights
Colorectal cancer (CRC) is a common gastrointestinal cancer accounting for ~6.1% of all cancer cases [1]
LncRNA SNHG15 is highly expressed in CRC tissues, which is associated with lymph node and liver metas‐ tases [7,8]
Statistical analyses revealed that high expression of LINC00963 was significantly associated with larger tumor size (P=0.039) and lymph node metastasis (P=0.020) of the patients (Table I)
Summary
Colorectal cancer (CRC) is a common gastrointestinal cancer accounting for ~6.1% of all cancer cases [1]. It is reported that CRC is a heterogeneous disease, and its occurrence and development is a multi‐step process, accom‐ panied by complicated changes at the molecular level [3]. Long non‐coding RNAs (lncRNAs) are incapable of encoding proteins and participate in regulating various biological processes [4,5,6,7,8]. Lnc‐GNAT1‐1 is downregulated in CRC, and it serves a tumor‐suppressive role by regulating Raf kinase inhibitor protein/NF‐κB/Snail signaling [6]. LINC00963 serves an important role in regulating the proliferation and migration of CRC cells [9]. The expression pattern, biological functions and underlying mechanism of LINC00963 in CRC have not been fully elucidated
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