Long noncoding RNA ZFPM2-AS1 is involved in lung adenocarcinoma via miR-511-3p/AFF4 pathway.

Lung cancer is the dominating cause of cancer-induced death and can be classified into small cell lung cancer and non-small cell lung cancer (NSCLC). Lung adenocarcinoma (LUAD) is the most common histological subtype of NSCLC and its pathology remains unclear. Mounting reports have revealed that lncRNAs could regulate cellular activities in cancers. Yet the role of ZFPM2 antisense RNA 1 (ZFPM2-AS1) in LUAD has not been elucidated. Using GEPIA online dataset, we identified the amplification of ZFPM2-AS1 in LUAD tissues. Through quantitative real-time reverse transcription-polymerase chain reaction analysis, we observed an upregulation of ZFPM2-AS1 in LUAD cell lines. Conducting loss-of-function assays, we found that ZFPM2-AS1 depletion impaired cell viability, suppressed cell migration, and reversed epithelial-mesenchymal transition progress in LUAD cells. Mechanism investigation manifested that ZFPM2-AS1 was distributed in the cytoplasm of LUAD cells. Moreover, ZFPM2-AS1 functioned as a molecular sponge of miR-511-3p, which was a suppressor in LUAD. Moreover, ZFPM2-AS1 sponged miR-511-3p and thereby deregulated AF4/FMR2 family member 4 (AFF4), a target of miR-511-3p. At length, rescue assays indicated that AFF4 overexpression revived the inhibiting effects of ZFPM2-AS1 knockdown on the biological processes in LUAD. All in all, this study uncovered the function and the mechanism of ZFPM2-AS1 in LUAD.

Li J ，Ge J ，Yang Y ，Liu B ，Zheng M ，Shi R ... -  《-》

LncRNA ZFPM2-AS1 promotes lung adenocarcinoma progression by interacting with UPF1 to destabilize ZFPM2.

Lung adenocarcinoma (LUAD), a histological subclass of non-small-cell lung cancer, is globally the leading cause of cancer-related deaths. Long noncoding RNAs (lncRNAs) are emerging as cancer regulators. Zinc finger protein multitype 2 antisense RNA 1 (ZFPM2-AS1) is an oncogene in gastric cancer, but its functions have not been investigated in LUAD. We showed that ZFPM2-AS1 expression is high in LUAD samples based on GEPIA database (http://gepia.cancer-pku.cn/) and validated ZFPM2-AS1 upregulation in LUAD cell lines. Functionally, ZFPM2-AS1 facilitated proliferation, invasion, and epithelial-to-mesenchymal transition of LUAD cells. Thereafter, we found that ZFPM2 was negatively regulated by ZFPM2-AS1, and identified the suppressive effect of ZFPM2 regulation by ZFPM2-AS1 on LUAD progression. Mechanistically, we showed that ZFPM2-AS1 interacted with up-frameshift 1 (UPF1) to regulate mRNA decay of ZFPM2. Rescue assays in vitro and in vivo confirmed that ZFPM2-AS1 regulated LUAD progression and tumor growth through ZFPM2. Taken together, our findings demonstrate a role for the ZFPM2-AS1-UPF1-ZFPM2 axis in LUAD progression, suggesting ZFPM2-AS1 as a new potential target for LUAD treatment.

Han S ，Cao D ，Sha J ，Zhu X ，Chen D ... -  《-》

Long Noncoding RNAs PTPRG Antisense RNA 1 Targets Cyclin D1 to Facilitate Cell Proliferation in Lung Adenocarcinoma.

Xue Y ，Diao M ，Lyu J ，Li K ，He L ，Chen J ，Li X ... -  《-》

PRKCZ-AS1 promotes the tumorigenesis of lung adenocarcinoma via sponging miR-766-5p to modulate MAPK1.

Wang M ，Liao Q ，Zou P 《-》

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

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.

Li W ，Zhang B ，Jia Y ，Shi H ，Wang H ，Guo Q ，Li H ... -  《Cancer Medicine》