Gastric adenocarcinoma (GAC) is a common, malignant type of tumor in human, and is accompanied with higher mortality. Muscleblind-like 3 (MBNL3) was found to be a pivotal participator in aggravating this cancer\'s progression. However, the regulatory effects of MBNL3 on GAC development have not been investigated. We therefore sought to study the functions of MBNL3 in GAC progression. In this study, it was demonstrated that MBNL3 exhibited higher expression, and GAC patients with higher MBNL3 expression had poor prognosis. Overexpression of MBNL3 facilitated, and knockdown of MBNL3 suppressed cell proliferation, invasion, and angiogenesis in GAC. Further experiments showed that miR-302e targets MBNL3. Rescue assays then uncovered that the miR-302e/MBNL3 axis aggravated GAC progression. In addition, MBNL3 activated the AKT/VEGFA pathway, and the suppressive regulatory impacts of MBNL3 knockdown on GAC cell proliferation, invasion, and angiogenesis could be rescued after 740 Y-P treatment. Through in vivo assay, it was proved that MBNL3 accelerated tumor growth in vivo. In conclusion, MBNL3 acted as a target of miR-302e to facilitate cell proliferation, invasion, and angiogenesis of gastric adenocarcinoma through the AKT/VEGFA pathway. Our findings illustrate that MBNL3 may be an available bio-target for GAC treatment.

Circular RNAs (circRNAs) play an important regulatory role in multiple human diseases, including organ allograft rejection. Infantile pneumonia (IP) is a common disease that seriously threatens the health of infants and young children. CircRNAs have been shown to be involved in the advance of IP. However, the function of circ_ZNF652 in IP has not been fully studied.
Lipopolysaccharide (LPS)-treated WI-38 cells were used as cell injury models of IP. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_ZNF652, miR-302e and Toll-like receptor 4 (TLR4). 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assay, thymidine analog 5-ethynyl-2\'-deoxyuridine (EdU) assay, and flow cytometry assay were utilized to explore cell functions. Western blot was employed to examine the protein levels of PCNA, Bcl-2, Bax, and TLR4. ELISA was used to detect the release of inflammatory cytokines. The relationship between miR-302e and circ_ZNF652 or TLR4 was verified by dual-luciferase reporter assay and RNA pull down assay.
Circ_ZNF652 was significantly up-regulated in serum of IP patients and LPS-induced WI-38 cells. Silencing circ_ZNF652 enhanced cell proliferation and inhibited cell apoptosis in LPS-induced WI-38 cells. MiR-302e was identified as a target of circ_ZNF652, and knockdown of circ_ZNF652 alleviated LPS-induced WI-38 cell injuries by up-regulating miR-302e. In addition, TLR4 was a downstream target of miR-302e. Overexpression of TLR4 recovered cell apoptosis and inflammation that were repressed by miR-302e enrichment in LPS-induced WI-38 cells.
Circ_ZNF652 regulates the expression of TLR4 by regulating miR-302e, thereby mediating cell proliferation, apoptosis and inflammation. The results provide a novel targeted therapy for IP.

OBJECTIVE: This study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).
METHODS: Bioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.
RESULTS: CXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors via activation of JAK-STAT signaling pathway.
CONCLUSIONS: CXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.

UNASSIGNED: MiRNA can be involved in regulating tumor genesis and development by regulating the expression of specific genes and regulating corresponding signaling pathways. In this study, we explored the function and mechanisms of miR-302e in glioma progression.
UNASSIGNED: Experimental methods include the following: real-time quantitative PCR, Western Blot Analysis, CCK8 assay and detection of apoptosis.
UNASSIGNED: MiR-302e was down-regulated in cancer tissues and cell lines, and the expression of miR-302e was negatively correlated with the tumor grade, which indicated poor prognosis in glioma patients. Followed functional analysis showed overexpression of miR-302e inhibited proliferation, migration and invasion but promoted apoptosis of glioma cells, while silencing miR-302e showed the opposite effects. Mechanistic studies have shown that VEGFA was a directed target of miR-302e. Forced expression of VEGFA removed the inhibiting impact of miR-302e on glioma development. In vivo tumorigenesis experiments showed that miR-302e suppressed glioma development by targeting VEGFA.
UNASSIGNED: Present study emphasized miR-302e suppressed glioma development by targeting VEGFA, which might be a valuable target for glioma treatment.

Long noncoding RNAs (lncRNAs), a group of transcripts, have been revealed to be critical participants in regulating multiple biological processes of malignant tumors. The knowledge of NPPA-AS1 (a new lncRNA) in cancer research is hardly known. Thus, it is of urgent need to study the underlying role of NPPA antisense RNA 1 (NPPA-AS1) in cervical cancer (CC). In this study, NPPA-AS1 was discovered to be lowly expressed and upregulation of it impaired cell proliferation and migration in CC. Besides, downregulation of it led to opposite results. Molecular mechanism assays uncovered that increased expression of NPPA-AS1 could inactivate Wnt/β-catenin signaling pathway in CC. In addition, NPPA-AS1 was found to negatively interact with miR-302e whereas positively correlate with dickkopf-1 (DKK1, an inhibitor of Wnt pathway) in CC. Besides, loss of function assay illuminated that miR-302e inhibition restrained cell proliferation and migration in CC. Subsequent rescue assays confirmed that NPPA-AS1 acted as a competing endogenous RNA in CC by sponging miR-302e to upregulate DKK1 expression. Finally, the RE-1 silencing transcription factor (REST) was testified to function as a transcription suppressor of NPPA-AS1 in CC. In brief, REST-repressed NPPA-AS1 regulates CC progression by modulating miR-302e/DKK1/Wnt/β-catenin signaling pathway.

Ovarian cancer is a leading cause of deaths due to gynaecological malignancy. While endogenous non-coding circular RNAs (circRNAs) in cancer have attracted attention, their roles in ovarian cancer are not known. We used qRT-PCR to quantify expression of circRhoC in ovarian cancer tissues and normal tissues. The effects of overexpressing or destruction of circRhoC on the phenotype of ovarian cancer cells were assessed both in vitro and in vivo. Dual-luciferase reporter assay assesses the microRNA sponge function of circRhoC. Western blotting was used to confirm the effects of circRhoC and microRNA on target gene expression. Our results showed that circRhoC was significantly up-regulated in ovarian cancer tissues compared to normal ovarian tissues. Overexpression of circRhoC in CAOV3 ovarian cancer cell increased cell viability, migration and invasion ability; destroying circRhoC in A2780 had the opposite effects and inhibited ovarian tumour cell A2780 dissemination in the peritoneum in vivo. We confirmed circRhoC functions as a sponge for miR-302e to positively regulate VEGFA; FISH experiments showed that circRhoC could co-focal with miR-302e; besides, overexpression of miR-302e reversed the ability of circRhoC to positively regulate VEGFA, and what\'s more, RIP assay showed that circRhoC could directly bind with VEGFA; besides, VEGFA expression level in ovarian cancer tissues was positively associated with circRhoC expression. In conclusion, the oncogenic effect of RhoC in ovarian cancer is at least in part due to circRhoC, which functions not only as a miR-302e sponge to positively regulate VEGFA protein expression, but may also directly bind and modulate VEGFA expression.

The biologic function as well as the mechanism of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) still remain largely unknown. Long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been reported to have a promotive effect on other human cancers, but its function in CRC still remains unknown. The expression levels of long noncoding RNA FGD5-AS1, CDCA7 mRNA, and miR-302e were assessed by RT-qPCR. The protein levels of CDCA7 were assessed by Western blot. The function of FGD5-AS1 was detected using cell viability assay, 5-ethynyl-2\'-deoxyuridine (EdU) assay, transwell, and caspase-3 activity assay. Additionally, the microRNAs (miRNAs) sponge potential of FGD5-AS1 was examined by RNA immunoprecipitation assay, RNA pull-down assay, and luciferase reporter assay. FGD5-AS1 was increased in colorectal cancer cell lines compared to normal cell lines. Inhibition of FGD5-AS1 suppressed cell proliferation, migration, invasion, and accelerated cell apoptosis in CRC. FGD5-AS1 competitively bound with miR-302e to modulate CDCA7. The inhibiting effects of FGD5-AS1 knockdown on CRC cell proliferation, migration, and invasion, and the promoting effects on CRC cell apoptosis could be revived by miR-302e suppression or CDCA7 upregulation. LncRNA FGD5-AS1 could promote CRC progression through sponging miR-302e and upregulating CDCA7. FGD5-AS1 might serve as a potential therapeutic target for CRC.

Cardiac hypertrophy (CH) is an adaptive cardiac response to overload whose decompensation eventually leads to heart failure or sudden death. Recently, accumulating studies have indicated the implication of long noncoding RNAs (lncRNAs) in CH progression. MAGI1-IT1 is a newly-identified lncRNA that is highly associated with CH, while its specific role in CH progression remains masked. In this study, we uncovered that MAGI1-IT1 was distinctly downregulated in angiotensin (Ang) II-induced hypertrophic H9c2 cells. Also, MAGI1-IT1 overexpression in Ang II-treated H9c2 cells strikingly abolished the enlarged surface area and the enhanced levels of hypertrophic markers such as ANP, BNP, and β-MHC. Mechanically, we found MAGI1-IT1 sponged miR-302e which was identified as a hypertrophy-facilitator here, and that miR-302e upregulation countervailed the inhibition of MAGI1-IT1 overexpression on hypertrophic cells. Moreover, it was confirmed that MAGI1-IT1 boosted DKK1 expression by absorbing miR-302e. Subsequently, we also illustrated that MAGI1-IT1 inactivated Wnt/beta-catenin signaling through a DKK1-dependent pathway. Finally, both the DKK1 inhibition and LiCI (Wnt activator) supplement abrogated the hypertrophy-suppressive impact of MAGI1-IT1 on Ang II-simulated hypertrophic H9c2 cells. Jointly, our findings disclosed that MAGI1-IT1 functioned as a negative regulator in CH through inactivating Wnt/beta-catenin pathway via targeting miR-302e/DKK1 axis, revealing a novel road for CH treatment.