LncRNA LOXL1‐AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR‐423‐5p and targeting MYBL2

Abstract

Lung adenocarcinoma (LUAD) is the most common form of malignant tumor and closely correlated with high risk of death worldwide. Accumulating researches have manifested that long noncoding RNAs (lncRNAs) are deeply involved in the progression of multiple cancers. LncRNA LOXL1 antisense RNA 1 (LOXL1‐AS1) was identified as an oncogene in several cancers, nonetheless, its biological effect and regulatory mechanism have not been explained in LUAD. Our present study suggested that LOXL1‐AS1 expression was considerably increased in LUAD tissues and cells. Moreover, LOXL1‐AS1 deficiency notably hampered cell proliferation and migration as well as dramatically facilitated cell apoptosis. Through molecular mechanism assays, LOXL1‐AS1 was identified as a cytoplasmic RNA and acted as a sponge of miR‐423‐5p. Furthermore, MYBL2 was targeted and negatively modified by miR‐423‐5p. Rescue experiments revealed that MYBL2 knockdown could counteract miR‐423‐5p repression‐mediated enhancement on the progression of LOXL1‐AS1 downregulated LUAD cells. More importantly, MYBL2 was discovered to interact with LOXL1‐AS1 promoter, indicating a positive feedback loop of LOXL1‐AS1/miR‐423‐5p/MYBL2 in LUAD. These findings manifested the carcinogenic role of LOXL1‐AS1 and LOXL1‐AS1/miR‐423‐5p/MYBL2 feedback loop in LUAD, which could be helpful to explore effective therapeutic strategy for LUAD patients.

TUSC8 inhibits the development of osteosarcoma by sponging miR‑197‑3p and targeting EHD2

“…Long non-coding RNAs (lncRNAs) are expressed in specific differentiated tissues or cancers (33)(34)(35). TUSC8 is a novel lncRNA, and its role in cancer progression is largely unknown.…”

LncRNA LOXL1-AS1 promotes esophageal squamous cell carcinoma progression by targeting DESC1

“…LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) is an antisense lncRNA, which is located at human chromosome 15 (q24.1) with 10781 bp [16]. The biological function of LOXL1-AS1 has been explored in various cancers, including osteosarcoma, prostate cancer, gastric cancer, glioblastoma, and breast cancer [17][18][19][20][21].…”

Functional mechanism and clinical implications of MicroRNA‐423 in human cancers

“…82 The positive feedback loop of lncRNA LOXL1 antisense RNA 1(LOXL1-AS1)/miR-423-5p/MYBL2 in lung adenocarcinoma is carcinogenic, and The high expression of LOXL1-AS1 competitively inhibits miR-423-5p expression and targets MYBL2 to promote proliferation and migration, and inhibit apoptosis of lung adenocarcinoma cell. 83 The highly expressed lncRNA NR2F1-AS1 regulates miR-423-5p/SRY-box 12 axis to promote papillary thyroid carcinoma cell proliferation and invasion. 84 Upregulation of LINC00319 has carcinogenic effects and enhances the expression of nucleus accumbens associated 1 (NACC1) by inhibiting miR-423-5p, which then promotes ovarian cancer cells metastasis and proliferation.…”