A novel lncRNA LOLA1 may predict malignant progression and promote migration, invasion, and EMT of oral leukoplakia via the AKT/GSK‐3β pathway

Abstract

Although dysregulation and dysfunction of long noncoding RNAs (lncRNAs) have been implicated in malignant behavior of oral squamous cell carcinoma (OSCC), whether aberrant lncRNAs play a role in the carcinogenesis of oral leukoplakia (OL) as the best-known precursor of OSCC remains undetermined. Differentially expressed lncRNAs in the occurrence and progression of OL were studied by microarray and quantitative reversetranscription polymerase chain reaction (qRT-PCR). We found a novel key lncRNA n386251 that we named LOLA1 (lncRNA oral leukoplakia progressed associated 1) in the OL progression. The results of qRT-PCR revealed that LOLA1 aberrant expression was validated in tissue samples and cell lines from the normal oral mucosa, OL to OSCC. Fluorescent in situ hybridization showed that LOLA1 expression localized predominately at the cytoplasm of Leuk1 cells. Cell function assays showed that LOLA1 significantly influenced cell migration, invasion, and epithelial-mesenchymal transition (EMT) protein expression. Potential mechanism experiments revealed that AKT/GSK-3β signaling was involved in the regulatory mechanism of LOLA1 in OL progression. Remarkably, Kaplan-Meier analysis revealed that LOLA1 overexpression could predict malignant events of OL progression to OSCC. In conclusion, the current study for the first time profiled and validated the key lncRNAs related to OL progression. Importantly, we demonstrated that a novel lncRNA LOLA1 upregulation was associated with OL malignant progression, suggesting LOLA1 may be a predictive biomarker. Moreover, LOLA1 may promote migration, invasion, and EMT process in OL malignant progression via AKT/GSK-3β pathway.

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

“…Moreover, valproic acid can enhance Snail expression, while it decreases E‐cadherin and GSK‐3β levels to stimulate EMT in breast tumor and to enhance their metastasis (Ozman et al, 2021). Another experiment reveals that lncRNA LOLA1 can induce Akt signaling to increase the migration and invasion in oral leukoplakia via EMT induction (W. Liu et al, 2021). Therefore, targeting such pathways can inhibit EMT‐mediated metastasis in tumor cells.…”

Type-2 epithelial-mesenchymal transition in oral mucosal nonneoplastic diseases

“…The findings demonstrate that EGFR and WNT pathway proteins are overexpressed in all OLK samples, triggered by chewing tobacco, and may be a risk factor for the type of proliferation. Remarkably, the lncRNA oral leukoplakia progressed associated 1(LOLA1) has been found to promote oral mucosa epithelial migration, invasion, and EMT via the AKT/GSK‐3β pathway, thereby accelerating the progression of OLK ( 24 ). Elevated levels of some novel biomarkers, such as Snail and Axin2, with a high correlation to OLK malignant transformation, can predict oral tumorigenesis ( 25 ).…”

Impact of Non-Coding RNAs on Chemotherapeutic Resistance in Oral Cancer

“…The expression of lncRNA-PNUTS is elevated and correlates with the mRNA level of ZEB1. A number of lncRNAs have been identified as EMT modulators in oral cancer [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ,…”