lncRNA mortal obligate RNA transcript was downregulated in ovarian carcinoma and inhibits cancer cell proliferation by downregulating miRNA-21.

microRNA-21 (miRNA-21) is a well-characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA-21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA-21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA-21, while miRNA-21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA-21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA-21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA-21.

Cinobufotalin Induces Ferroptosis to Suppress Lung Cancer Cell Growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC Pathway via Resibufogenin.

BACKGROUND: Lung cancer is the leading cause of cancer-associated death and the first most diagnosed cancer in the world. More than 2 million new cases are diagnosed and 1.6 million people die due to lung cancer every year. It is urgent to explore novel drugs and approaches for lung cancer treatment. Cinobufotalin is a TCM isolated from dried toad venom, which has been used to treat lung cancer. However, the precise mechanism remains unclear. OBJECTIVE: This study was to investigate the mechanism of cinobufotalin treated in lung cancer. METHODS: Cell growth was identified by Cell Counting Kit-8 (CCK-8) assay. Besides, ferroptosis of lung cancer cells was determined by intracellular iron content, lactate dehydrogenase (LDH) release and mitochondrial membrane potential. Moreover, RNA levels and proteins were detected by quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB), respectively. In addition, the regulatory effect of hsa-miR-367-3p on TFRC was confirmed by luciferase reporter assay. RESULTS: This study indicated that cinobufotalin suppressed lung cancer cell growth through resibufogenin. Besides, cinobufotalin induced ferroptosis in lung cancer cells through resibufogenin. Moreover, cinobufotalin increased lncRNA LINC00597 level, whereas it downregulated hsa-miR-367-3p expression in lung cancer cells via resibufogenin. In addition, ferroptosis inducer transferrin receptor (TFRC) was the target of hsa-miR-367-3p, and lncRNA LINC00597 upregulates TFRC expression through sponging hsa-miR-367-3p in lung cancer cells. CONCLUSION: In summary, this study indicated that cinobufotalin induced ferroptosis to suppress lung cancer cell growth by lncRNA LINC00597/hsa-miR-367-3p/TFRC pathway via resibufogenin might provide novel therapeutic targets for lung cancer therapy.

Down-regulated NEDD4L facilitates tumor progression through activating Notch signaling in lung adenocarcinoma.

Neural precursor cell expressed developmentally down-regulated 4-like protein (NEDD4L), an E3 ubiquitin ligase, exerts an important role in diverse biological processes including development, tumorigenesis, and tumor progression. Although the role of NEDD4L in the pathogenesis of lung adenocarcinoma (LUAD) has been described, the mechanism by which NEDD4L promotes LUAD progression remains poorly understood. In the study, the correlation between NEDD4L level and clinical outcome in LUAD patients was analysed using the data from The Cancer Genome Atlas (TCGA) database. NEDD4L expression in LUAD cell lines and tissue samples was assessed through quantitative real-time PCR (qRT-PCR). The biological function of NEDD4L on regulating LUAD cell proliferation was tested with Cell Counting Kit-8 (CCK-8) assay in vitro, and mouse xenograft tumor model in vivo. We found that NEDD4L expression was significantly decreased in LUAD tissues and cell lines. Lower expression of NEDD4L exhibited a significantly poorer overall survival. Functionally, NEDD4L knockdown in H1299 cells accelerated cell growth, whereas NEDD4L overexpression in A549 cells repressed cell proliferation. NEDD4L overexpression also inhibited tumor xenograft growth in vivo. Mechanistically, NEDD4L decreased the protein stability of notch receptor 2 (Notch2) through facilitating its ubiquitination and degradation by ubiquitin-proteasome system. Consequently, NEDD4L negatively regulated Notch signaling activation in LUAD cells, and RO4929097 (a Notch inhibitor) treatment effectively repressed the effect of NEDD4L knockdown on LUAD cell proliferation. Taken together, these results demonstrate that down-regulated NEDD4L facilitates LUAD progression by activating Notch signaling, and NEDD4L may be a promising target to treat LUAD.