Silencing LINC01116 suppresses the development of lung adenocarcinoma via the AKT signaling pathway

Abstract

Background: A growing body of evidence has proven that long noncoding ribonucleic acids (lncRNAs) are important epigenetic regulators that play crucial parts in the pathogenesis of human cancers. Previous studies have shown that long intergenic nonprotein coding RNA 01116 (LINC01116) is a carcinogen in several carcinomas; however, its function in lung adenocarcinoma (LUAD) has not been clarified. Here, we aimed to investigate the role of LINC01116 in LUAD. Methods: The relative expression levels of LINC01116 in LUAD cell lines and tissues were detected by quantitative reverse transcription polymerase chain reaction. A Kaplan-Meier survival analysis was performed using patient information from the Gene Expression Profiling Interactive Analysis (GEPIA) database. LUAD proliferation, invasion, migration, and apoptosis were measured by performing cell counting kit-8, colony formation, transwell, wound healing, and flow cytometric assays. A xenograft animal experiment was performed to investigate the effect of LINC01116 in vivo. Protein kinase B (AKT) signaling pathway-related protein expressions were tested by Western blot assay. Results: LINC01116 expression was upregulated in LUAD cells and tissues. The lossof-function experiments on LUAD cells revealed that silencing LINC01116 expression could decrease cell viability both in vitro and in vivo. Furthermore, silencing LINC01116 inhibited LUAD cell invasion and migration and induced cell apoptosis. Mechanically, silencing LINC01116 significantly decreased p-AKT protein levels, and an AKT pathway stimulator could rescue the suppressive effects of small interfering LINC011116-specific RNAs on LUAD development. Conclusions: Our study demonstrated that silencing LINC01116 suppresses the development of LUAD via the AKT signaling pathway.

Promising Advances in LINC01116 Related to Cancer

“…For instance, recent studies showed that a considerable number of patients with low expression of LINC01116 were generally diagnosed with TNM I rather than TNM I/III. These results indicate that LINC01116 can be considered as a latent regulator that participates in the progression of metastasis and invasiveness in LC ( Shang et al, 2021 ). Additionally, silencing of LINC01116 reverses this effect.…”

Identification of an autophagy-related 12-lncRNA signature and evaluation of NFYC-AS1 as a pro-cancer factor in lung adenocarcinoma

“…It has been shown that LINC00857 enhances BIRC5-dependent radio-sensitivity of cancer cells (Han et al, 2020), regulates apoptosis and glycolysis (Wang et al, 2020b), and is identified as one of the prognostic markers for the early stage lung adenocarcinoma (Mu et al, 2021). LINC01116 is oncogenic in several other kinds of tumors (Hu et al, 2018;Chen et al, 2020;Wu et al, 2020;Ye et al, 2020) and promotes lung adenocarcinoma proliferation and metastasis possibly via the Akt pathway (Zeng et al, 2020;Shang et al, 2021;Wu et al, 2021). The prognostic function of LINC00996 is also implicated in colorectal cancer (Ge et al, 2018), head and neck cancer (Ge et al, 2018), and multiple myeloma (Zhou et al, 2020).…”

Construction of an algorithm based on oncosis‐related LncRNAs comprising the molecular subtypes and a risk assessment model in lung adenocarcinoma

“… 27 LINC01116 functioned as a competing endogenous RNA (ceRNA) to bind with miR‐744‐5p, regulate the downstream CDCA4 expression, and accelerate proliferation, migration, invasion, and cisplatin resistance of LUAD cell lines, 28 , 29 which could be blocked by the AKT signaling pathway. 30 LINC00324 acted as a ceRNA to interact with miR‐139‐5p and down‐regulated its expression, which accelerated the cell proliferation and invasion of NSCLC cell lines. 31 Pan et al 32 have also proved that LINC00324 promoted the proliferation and metastasis of LUAD tissues and cells by the miR‐615‐5p/AKT1 pathway.…”

“…Up‐regulated LINC01137 enhanced the malignant tendency of oral squamous cell carcinoma cells and promoted the malignant transformation of oral cells 27 . LINC01116 functioned as a competing endogenous RNA (ceRNA) to bind with miR‐744‐5p, regulate the downstream CDCA4 expression, and accelerate proliferation, migration, invasion, and cisplatin resistance of LUAD cell lines, 28,29 which could be blocked by the AKT signaling pathway 30 . LINC00324 acted as a ceRNA to interact with miR‐139‐5p and down‐regulated its expression, which accelerated the cell proliferation and invasion of NSCLC cell lines 31 …”