Silencing LncRNA CASC9 inhibits proliferation and invasion of colorectal cancer cells by MiR-542-3p/ILK

Abstract

Colorectal cancer (CRC) ranks the third in cancers and the second in the reasons of cancer-related death. More evidence indicates that long non-coding RNA participates in tumor initiation and progression. It’s known that cancer susceptibility candidate 9 is an oncogenic long non-coding RNA in CRC. miR-542-3p is a negative regulator of CRC, while integrin-linked kinase could contribute to tumor progression and chemoresistance. However, the correlation among long non-coding RNA cancer susceptibility candidate 9, miR-542-3p and integrin-linked kinase in CRC is still unclear. We demonstrated long non-coding RNA cancer susceptibility candidate 9 in CRC specimens and cell lines overexpressed via real-time quantitative polymerase chain reaction. Once long non-coding RNA cancer susceptibility candidate 9 was knocked down, it significantly inhibited proliferation, invasion, and migration of CRC cells in real-time quantitative polymerase chain reaction, cell counting kit-8, 5-ethynyl-2’-deoxyuridine, and transwell assays, which also was validated in vivo. Long non-coding RNA cancer susceptibility candidate 9 negatively regulates miR-542-3p in a targeted manner, and the function of up-regulated miR-542-3p was confirmed similarly. While miR-542-3p negatively regulates integrin-linked kinase. Thus, we further verified that overexpression of integrin-linked kinase on down-regulated long non-coding RNA cancer susceptibility candidate 9 or up-regulated miR-542-3p significantly restored CRC cell proliferation via bioinformatic analysis, dual-luciferase report assay, real-time quantitative polymerase chain reaction, RNA immunoprecipitation, and western blot. This study testified that silencing long non-coding RNA cancer susceptibility candidate 9 could inhibit proliferation and invasion of CRC cells by miR-542-3p/integrin-linked kinase.

Disulfidptosis-related Long Non-Coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma

“…Prior studies have revealed a strong correlation of CASC9 with hepatocellular carcinoma, breast cancer, osteosarcoma, and pancreatic cancer progression[26-29] and its role in enhancing tumor resistance to ge tinib and gemcitabine [30][31][32]. However, Liu and Zhang et al noted contrasting ndings and reported that CASC9 silencing suppressed colon cancer cell proliferation and invasion [33,34]. The risk signature for cuproptosis in colon cancer patients includes ZEB1-AS1 and SNHG7 [35,36], while ATP2A1-AS1 was incorporated into the lncRNA-based prognosis prediction model for cuproptosis in patients with cervical cancer [37].…”

The functions and mechanisms of long non-coding RNA in colorectal cancer

“…BBOX1-AS1 promotes the progression of CRC by acting as a sponge for hsa-miR-361-3p and upregulating SH2B1 ( 75 ). Silencing CASC9 can not only downregulate AKT3 expression by reducing the competitive binding of CASC9 with miR-576-5p, thereby inhibiting CRC cell proliferation ( 210 ), it can also inhibit the proliferation of CRC cells through the miR-542-3p/integrin-linked kinase pathway ( 80 ), CCAT2 is highly overexpressed in microsatellite stable CRC and can enhance tumor growth by activating the WNT signaling pathway through the CCAT2/miR-17-5p/TCF7L2 axis ( 86 ). Studies have found that by overexpressing or knocking down CCAT2, reducing CCAT2 can increase miR-145, thereby inhibiting the proliferation of cancer cells ( 211 ).…”

“…Zhang et al. discovered that the CASC9/miR-542-3p/integrin-linked kinase regulatory axis is involved in the invasion and migration of CRC cells ( 80 ). The upregulation of CCAT1 expression promotes cell proliferation and invasion ( 83 ).…”

Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

“…The lncRNAs cancer susceptibility candidate 9 (CASC9) and small nucleolar RNA host gene 6 (SNHG6) can positively regulate the TGF-β pathway in CRC. CASC9, in particular, increases the stabilization of TGF-β2 mRNA[ 75 ], and a study by Zhang et al [ 76 ] showed that it targets miRNA-542-3p and could also increase chemoresistance. The lncRNA SNHG6, on the other hand, targets miR-26a-5p and increases the resistance of CRC cells to 5-fluorouracil (5-FU).…”