miR‑802 inhibits the aggressive behaviors of non‑small cell lung cancer cells by directly targeting FGFR1

Molecular Carcinogenesis

et al. 2020

Gastric cancer (GC) is one of the most common malignancies of the digestive system worldwide. Multiple long noncoding RNAs (lncRNAs) participate in the regulation of GC development and metastasis. In this study, we aimed to elucidate the expression and function of lncRNA IGFL2‐AS1 in GC. We found that IGFL2‐AS1 was highly expressed in GC tissues and cell lines. Knockdown of IGFL2‐AS1 suppressed GC cell proliferation, migration, and invasion in vitro. Furthermore, we identified that IGFL2‐AS1 exerted its function as a molecular sponge of miR‐802. MiR‐802 was demonstrated to be a tumor suppressor, and overexpression of miR‐802 suppressed GC cell growth, migration, and invasion. Mechanistically, we revealed that the cAMP‐regulated phosphoprotein 19 (ARPP19) was a direct target of miR‐802 and could reverse the inhibitory function of miR‐802. Moreover, our results confirmed that knockdown of IGFL2‐AS1 inhibited GC tumor development in an in vivo GC tumor xenograft model. In summary, our data suggest that the IGFL2‐AS1/miR‐802/ARPP19 axis plays a critical role in the progression and metastasis of GC. Therapies targeting the IGFL2‐AS1/miR‐802/ARPP19 axis can potentially improve GC treatment.

Section: Discussionsupporting

confidence: 86%

“…Zhang et al 34 reported that miR-802 promoted cell proliferation and inhibited cell apoptosis in human cervical cancer. 33 MiR-802 also suppressed non-small cell lung cancer development by regulating FGFR1.…”

Section: Discussionmentioning

confidence: 99%

LncRNA IGFL2‐AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR‐802 in gastric cancer

Molecular Carcinogenesis

et al. 2020

“…It has been reported that miR-377 expression is remarkably downregulated in NSCLC tissues, and thus contributing to inhibited cell proliferation and development as a tumor-suppressor gene. 11,18 Similarly, our experimental data suggested that miR-377-5p was significantly reduced in vivo and in cell models, and lessened cell viability, proliferation, migration, and invasion. Furthermore, we observed that miR-377-5p overexpression-induced cell-cycle arrest, the numbers of G0/G1-phase cells were increased and that of S-phase cells were reduced, which were consistent with previous studies.…”

Section: Discussionsupporting

confidence: 59%

“…To date, several miRNAs have been reported to inhibit cell metastasis by targeting AKT1 in cancers. 17,18 However, the effects and regulation mechanisms between miR-377 and AKT1 has not been elucidated. To investigate the effects of miR-377-5p and/or AKT1 on the development, invasion, and metastasis of lung carcinoma, we measured their expressions in cancer tissues.…”

Section: Introductionmentioning

confidence: 99%

miR‐377‐5p inhibits lung cancer cell proliferation, invasion, and cell cycle progression by targeting AKT1 signaling

J of Cellular Biochemistry

Shi

et al. 2018

Lung carcinoma is the most common type of malignant tumors globally, and its molecular mechanisms remained unclear. With the aim to investigate the effects of microRNA (miR)‐377‐5p on the cell development, invasion, metastasis, and cycle of lung carcinoma, this study was performed. We evaluated miR‐377‐5p expression levels in lung cancer tissues and cell models. Cell viability, proliferation, migration, invasion abilities, and cell cycle distribution were measured using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, crystal violet, transwell, and flow cytometry assay. Furthermore, expression levels of protein kinase B α subunit (AKT1) and proteins related to cell cycle and epithelial‐mesenchymal transition (EMT) were assessed using Western blot analysis and quantitative real‐time polymerase chain reaction. These results suggested that miR‐377‐5p was downregulated in vivo and in cell models, and miR‐377‐5p overexpression inhibited cell viability, proliferation, migration, invasion, and induced cell‐cycle arrest. In addition, as a target of miR‐377‐5p, AKT1 alleviated the decreases of cell viability, proliferation, migration, invasion, the S‐phase cells, the expression of cyclin D1, fibronectin, and vimentin, as well as the increases of the G0/G1‐phase cells, the expression of Foxo1, p27 kip1, p21 Cip1 and E‐cadherin when miR‐377‐5p overexpressed. In conclusion, miR‐377‐5p inhibited cell development and regulated cell cycle distribution and EMT by targeting AKT1, which provided a theoretical basis for further study of lung carcinoma therapeutics.

“…Previous research has shown that overexpression of Cdk6 promoted the progression of lung adenocarcinoma, 48 and downregulation of Cdk6 inhibited the progression of NSCLC. 49 The present study demonstrated that HNF1A-AS1 promoted the progression of NSCLC via upregulation of Cdk6. In addition, due to the complicated molecular mechanism of NSCLC progression, the effects of HNF1A-AS1 on epithelial-mesenchymal transition, autophagy or apoptosis of NSCLC need to be further explored.…”

Section: Discussionsupporting

confidence: 53%

lncRNA HNF1A‐AS1 modulates non–small cell lung cancer progression by targeting miR‐149‐5p/Cdk6

J of Cellular Biochemistry

Chen

et al. 2019

Growing evidence have shown the important regulation of lncRNAs (long noncoding RNAs) in non–small cell lung cancer (NSCLC). lncRNA hepatocyte nuclear factor 1 homeobox A (HNF1A)‐antisense RNA 1 (AS1), an “oncogene”, was reported to regulate human tumors progression. However, the molecular mechanism of HNF1A‐AS1 involved in the development of NSCLC is still under investigation. In the current study, we found that HNF1A‐AS1 was relatively upregulated in both NSCLC patient tissues and cell lines. Functional studies established that overexpression of HNF1A‐AS1 promoted cell proliferation, cell cycle, invasion, and migration of NSCLC cells in vitro. The promotion abilities of HNF1A‐AS1 on NSCLC cell progression were suppressed via knockdown of HNF1A‐AS1. miR‐149‐5p was then proved to be a novel target of HNF1A‐AS1, whose expression was negatively correlated with HNF1A‐AS1 in NSCLC patient tissues and cell lines. HNF1A‐AS1 increased the expression of cyclin‐dependent kinase 6 (Cdk6) via sponging with miR‐149‐5p. Gain‐ and loss‐of‐functional studies indicated that HNF1A‐AS1 promoted NSCLC progression partially through inhibition of miR‐363‐3p and induction of Cdk6. Subcutaneous xenotransplanted tumor model confirmed that interference of HNF1A‐AS1 suppressed the tumorigenic ability of NSCLC via upregulation of miR‐149‐5p and downregulation of Cdk6 in vivo. In conclusion, our findings clarified the biologic significance of the HNF1A‐AS1/miR‐149‐5p/Cdk6 axis in NSCLC progression and provided novel evidence that HNF1A‐AS1 may be a new potential therapeutic target for the treatment of NSCLC.