Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. In this study, we found that RBP Mex3a was significantly upregulated in LUAD tissues and elevated Mex3a expression was associated with poor LUAD prognosis and metastasis. Furthermore, we demonstrated that Mex3a knockdown significantly inhibited LUAD cell migration and invasion in vitro and metastasis in nude mice. Transcriptome sequencing indicated that Mex3a affected gene expression linked to ECM-receptor interactions, including laminin subunit alpha 2(LAMA2). RNA immunoprecipitation (RIP) assay revealed Mex3a directly bound to LAMA2 mRNA and Mex3a increased the instability of LAMA2 mRNA in LUAD cells. Furthermore, we discovered that LAMA2 was surprisingly downregulated in LUAD and inhibited LUAD metastasis. LAMA2 knockdown partially reverse the decrease of cell migration and invasion caused by Mex3a knockdown. In addition, we found that both Mex3a and LAMA2 could influence PI3K-AKT pathway, which are downstream effectors of the ECM-receptor pathway. Moreover, the reduced activation of PI3K-AKT pathway in caused by Mex3a depletion was rescued by LAMA2 knockdown. In conclusion, we demonstrated that Mex3a downregulates LAMA2 expression to exert a prometastatic role in LUAD. Our study revealed the prognostic and prometastatic effects of Mex3a in LUAD, suggesting that Mex3a can serve as a prognostic biomarker and a target for metastatic therapy.

Background Although Mex3 RNA‐binding family member A (Mex3a) has demonstrated an important role in multiple cancers, its role and regulatory mechanism in CRC is unclear. In this study, we aimed to investigate the role and clinical significance of Mex3a in CRC and to explore its underlying mechanism. Methods Western blotting and quantitative real‐time polymerase chain reaction (qRT‐PCR) were performed to detect the expression levels of genes. 5‐Ethynyl‐2'‐deoxyuridine (EDU) and transwell assays were utilized to examine CRC cell proliferation and metastatic ability. The R software was used to do hierarchical clustering analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Overexpression and rescue experiments which included U0126, a specific mitogen activated protein kinase kinase/extracellular regulated protein kinase (MEK/ERK) inhibitor, and PX‐478, a hypoxia‐inducible factor 1 subunit alpha (HIF‐1α) inhibitor, were used to study the molecular mechanisms of Mex3a in CRC cells. Co‐immunoprecipitation (Co‐IP) assay was performed to detect the interaction between two proteins. Bioinformatics analysis including available public database and Starbase software (starbase.sysu.edu.cn) were used to evaluate the expression and prognostic significance of genes. TargetScan (http://www.targetscan.org) and the miRDB (mirdb.org) website were used to predict the combination site between microRNA and target mRNA. BALB/c nude mice were used to study the function of Mex3a and hsa‐miR‐6887‐3p in vivo. Results Clinicopathological and immunohistochemical (IHC) studies of 101 CRC tissues and 79 normal tissues demonstrated that Mex3a was a significant prognostic factor for overall survival (OS) in CRC patients. Mex3a knockdown substantially inhibited the migration, invasion, and proliferation of CRC cells. Transcriptome analysis and mechanism verification showed that Mex3a regulated the RAP1 GTPase activating protein (RAP1GAP)/MEK/ERK/HIF‐1α pathway. Furthermore, RAP1GAP was identified to interact with Mex3a in Co‐IP experiments. Bioinformatics and dual‐luciferase reporter experiments revealed that hsa‐miR‐6887‐3p could bind to the 3'‐untranslated regions (3'‐UTR) of the Mex3a mRNA. hsa‐miR‐6887‐3p downregulated Mex3a expression and inhibited the tumorigenesis of CRC both in vitro and in vivo. Conclusions Our study demonstrated that the hsa‐miR‐6887‐3p/Mex3a/RAP1GAP signaling axis was a key regulator of CRC and Mex3a has the potential to be a new diagnostic marker and treatment target for CRC.

Autophagy is a ubiquitous process used widely across plant cells to degrade cellular material and is an important regulator of plant growth and various environmental stress responses in plants. The initiation and dynamics of autophagy in plant cells are precisely controlled according to the developmental stage of the plant and changes in the environment, which are transduced into intracellular signaling pathways. These signaling pathways often regulate autophagy by mediating TOR (Target of Rapamycin) kinase activity, an important regulator of autophagy initiation; however, some also act via TOR-independent pathways. Under nutrient starvation, TOR activity is suppressed through glucose or ROS (reactive oxygen species) signaling, thereby promoting the initiation of autophagy. Under stresses, autophagy can be regulated by the regulatory networks connecting stresses, ROS and plant hormones, and in turn, autophagy regulates ROS levels and hormone signaling. This review focuses on the latest research progress in the mechanism of different external signals regulating autophagy.

Background We have previously developed a unique metastasis‐associated signature consisting of six long non‐coding RNAs (lncRNAs), including a novel lncRNA, namely LINC02323. In the present study, we aimed to investigate the underlying roles of LINC02323 in the migration, invasion and TGF‐β‐induced epithelial‐mesenchymal transition (EMT) of lung adenocarcinoma (LUAD) cells. Methods The distribution of LINC02323 was detected by the nuclear‐plasma separation experiment. Cell proliferation was assessd by MTT assay, and cell migration and invation were detected by transwell assays. EMT was detected by RT‐qPCR and western blotting. Interaction between miRNA and LINC02323 was predicted by starBase v2.0 and confirmed by the double luciferase reporting system. Results LINC02323 was distributed in the cytoplasm and nucleus. The overexpression or deletion of LINC02323 did not affect the proliferation of LUAD cells, while significantly affected the migration and invasion of LUAD cells. TGF‐β‐induced EMT process was significantly affected by both RNA interference (RNAi) and overexpression of LINC02323. The predicted results showed that there were binding sites between LINC02323 and miR‐1343‐3p. The expression of LINC02323 was found to be negatively correlated with miR‐1343‐3p in LUAD by analyzing The Cancer Genome Atlas (TCGA) database. The double luciferase reporting system, RT‐qPCR and western blotting experiments confirmed that LINC02323 could bind to miR‐1343‐3p, which bound to TGF‐β receptor 1 (TGFBR1). Inhibition of miR‐1343‐3p reversed LINC02323 silencing‐mediated suppression of migration, invasion and EMT. Conclusions LINC02323 acts as a competing endogenous RNA (ceRNA), which sponged miR‐1343‐3p to upregulate the TGFBR1 expression and promote the EMT and metastasis in LUAD. Key points Significant findings of the study LINC02323 promotes epithelial‐mesenchymal transition and metastasis via sponging miR‐1343‐3p in lung adenocarcinoma. What this study adds LINC02323 is a key molecule in the process of invasion and metastasis of LUAD and might be used as a potential target in metastatic cancer.

Background Local relapses and metastases are primary causes of death in lung cancer patients. In the present study, we aimed to develop a prognostic signature based on metastasis‐associated lncRNAs in patients with lung adenocarcinoma (LUAD). Methods Firstly, the potential metastasis‐associated lncRNAs were identified by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA), and based on which, an lncRNA signature was constructed for prediction of relapse in LUAD patients using Cox proportional hazards regression analysis. Moreover, the prognostic performance of the lncRNA signature was evaluated using Kaplan‐Meier survival analysis, time‐dependent receiver operating characteristic (ROC) curve and Cox analysis, respectively. In addition, the potential metastasis‐associated function of these six lncRNAs was confirmed by lncRNA over‐expression or depletion and in vitro transwell assays in LUAD cells. Results An lncRNA signature consisting of six most important prognostic factors (LINC01819, ZNF649‐AS1, HNF4A‐AS1, FAM222A‐AS1, LINC02323 and LINC00672) was developed. The signature was an independent predictor for patients' relapse‐free survival (RFS), which could provide higher tumor relapse prediction capability compared with the TNM staging system at three years and five years, respectively (P = 0.0209 and P = 0.0468). Furthermore, the combination of this lncRNA signature and TNM stage had better prognostic value than TNM stage alone at three and five years, respectively (P = 0.0006 and P = 0.0096). Additionally, all the lncRNAs of the signature had a regulatory role in the LUAD cell mobility. Conclusions This novel six‐lncRNA signature had considerable prognostic value for prediction of relapse in LUAD patients. Key points Significant findings of the studyThe unique metastasis‐associated lncRNA signature was related to tumor metastasis and prognosis in LUAD patients. What this study addsThis signature had considerable prognostic value for prediction of relapse in LUAD patients.