LncRNA AC099850.3 promotes hepatocellular carcinoma proliferation and invasion through PRR11/PI3K/AKT axis and is associated with patients prognosis

Abstract

Background: LncRNA is a key factor influencing tumor development. The present study aimed to investigate the effect of a novel lncRNA on the progression of hepatocellular carcinoma (HCC). Methods: A candidate lncRNA in The Cancer Genome Atlas database was identified using limma and survival R packages. The effect of lncRNA AC099850.3 on cell proliferation, apoptosis, migration, and invasion, as well as its association with immune cells in HCC were investigated. Furthermore, the functional mechanisms of lncRNA AC099850.3 in HCC were elucidated. Results:The aberrant expression of lncRNA AC099850.3 was identified in tumor tissues and its prognostic relevance in HCC was determined. The results revealed that AC099850.3 was highly expressed in HCC tissues and cell lines, and it predicted poor prognosis in patients with HCC. Furthermore, knockdown of AC099850.3 significantly suppressed the proliferation and metastatic potential of HCC cells, and promoted cell apoptosis in HCC cells. The results of gene set enrichment analysis revealed that the PI3K/AKT pathway was associated with the biological function of AC099850.3, which was further validated by western blotting. PRR11 was identified as the target gene of AC099850.3 and we established that AC099850.3 acted as an oncogene in the PRR11/PI3K/AKT axis. Immune cell infiltration analyses results revealed that AC099850.3 was positively correlated with T follicular helper cells, M0 macrophages, CD4 + memory T cells, and memory B cells. Conversely, AC099850.3 was negatively correlated with M2 macrophages, monocytes, natural killer cells, and CD8 + T cells, which could be responsible for its oncogenic effect. Of note, a significantly positive correlation was observed between AC099850.3 and key immune checkpoint molecules (PD-1, PD-L1, PD-L2, and CTLA4) in the present study, making AC099850.3 a potential immune therapeutic target for HCC. Conclusion: AC099850.3 can promote malignant biological behavior of HCC cells, and could be a potential biomarker and therapeutic target for HCC.

Establishment of Prognostic Signatures of N6-Methyladenosine-Related lncRNAs and Their Potential Functions in Hepatocellular Carcinoma Patients

“…Among the prognosis-related lncRNAs in HCC, SNHG3, SNHG4, and NRAV have been reported to function in bladder cancer ( 46 ), non-small cell lung cancer ( 47 ), osteosarcoma ( 48 ), colorectal cancer ( 49 ), breast cancer ( 50 ), gastric cancer ( 51 ), and glioma ( 52 ) through interactive molecular pathway studies. However, other lncRNAs, such as AC099850.4 ( 53 ), MKLN1-AS ( 54 , 55 ), and C2orf27A ( 56 ) have been reported in HCC. POLH-AS1 POLH-AS1 have not been reported in HCC and we detected its expression of HCC tissues in BCLC stage A and BCLC stage C by RT-PCR.…”

An m6A/m5C/m1A/m7G-Related Long Non-coding RNA Signature to Predict Prognosis and Immune Features of Glioma

“…The m6A/m5C/m1A/m7G-LS was shown to have predictive significance and was then used to identify prognostic characteristics. The lncRNA, AC099850.3, promotes hepatocellular carcinoma proliferation and invasion through the PRR11/PI3K/AKT axis and is associated with patient prognosis ( Zhong et al, 2022 ), indicating that it is an important prognostic indicator. The lncRNA, SOX21-AS1, is hypomethylated in cervical cancer, can serve as a new biomarker for the diagnosis of cervical squamous cell carcinoma, and is a potential therapeutic target.…”

Construction of a necroptosis‐related lncRNA signature to predict the prognosis and immune microenvironment of head and neck squamous cell carcinoma

“…It promotes tumor cell proliferation and invasion through the PRR11/PI3K/AKT axis in hepatocellular carcinoma. 28 Besides, this lncRNA is also considered a prognostic biomarker in non‐small‐cell lung cancer and colorectal cancer patients. 29 , 30 Moreover, as shown in the Sankey diagram, several lncRNA‐related genes were considered to act important roles in tumor biological processes.…”

“…In addition, the lncRNA AC099850.3 was determined to display a crucial role in the biological progression of multiple tumors. It promotes tumor cell proliferation and invasion through the PRR11/PI3K/AKT axis in hepatocellular carcinoma 28 . Besides, this lncRNA is also considered a prognostic biomarker in non‐small‐cell lung cancer and colorectal cancer patients 29,30 …”