Long non-coding RNA OIP5-AS1 promotes pancreatic cancer cell growth through sponging miR-342-3p via AKT/ERK signaling pathway

Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1), a long non-coding RNA (lncRNA), has been reported to link with the progression of some cancers. However, its biological functions and underlying molecular mechanisms in pancreatic cancer are largely unknown. The aim of this study was to investigate the role of lncRNA OIP5-AS1 in pancreatic cancer. Quantitative real-time PCR analysis revealed that OIP5-AS1 is highly expressed in pancreatic cancer tissues versus adjacent non-tumor tissues. In vitro functional assays showed that downregulation of OIP5-AS1 or overexpression of miR-342-3p inhibited the proliferation, decreased Ki67 expression, and induced cell cycle arrest in pancreatic cancer cells. The expression of cyclinD1, CDK4, and CDK6 was decreased by knockdown of OIP5-AS1. Moreover, we found that OIP5-AS1 acted as a miR-342-3p sponge to suppress its expression and function. Dual-luciferase assay confirmed the interaction of OIP5-AS1 and miR-342-3p and verified anterior gradient 2 (AGR2) as a direct target of miR-342-3p. Results showed that depletion of miR-342-3p abolished the inhibitory effects of OIP5-AS1 knockdown on pancreatic cancer cell growth. The expression of Ki67, AGR2, cyclinD1, CDK4, CDK6, p-AKT, and p-ERK1/2 was reversed by silencing of miR-342-3p in pancreatic cancer cells with OIP5-AS1 knockdown. Further, knockdown of OIP5-AS1 suppressed tumor growth in a xenograft mouse model of pancreatic cancer. OIP5-AS1 induced pancreatic cancer progression via activation of AKT and ERK signaling pathways. Therefore, we demonstrate that OIP5-AS1 functions as oncogene in pancreatic cancer and its downregulation inhibits pancreatic cancer growth by sponging miR-342-3p via targeting AGR2 through inhibiting AKT/ERK signaling pathway.

     

Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p/CDK6 axis

Journal of Physiology and Biochemistry - Emerging evidence has suggested that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is upregulated in hepatocellular...     

Long non-coding RNA PVT1-5 promotes cell proliferation by regulating miR-126/SLC7A5 axis in lung cancer

Dysregulated long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA plasmacytoma variant translocation 1 (PVT1) is reported to be an oncogene in a variety of cancers. However, the roles of PVT1-5 and its related miRNAs in lung cancer are poorly understood. In this study, we found that PVT1-5 expression was significantly increased in lung cancer tissues and cell lines. By using biotin-labeled lncRNA-PVT1-5 probe for miRNA in vivo precipitation (miRIP) in lung cancer cells and dual-luciferase reporterassays, we identified that miR-126 was associated with lncRNA-PVT1-5. Furthermore, knockdown of lncRNA-PVT1-5 in cells could down-regulate the expression of SLC7A5, the target of oncogenic miR-126, resulting in the cell proliferation. Conversely, inhibiting the expression of miR-126 markedly increased the expression of SLC7A5 and alleviated cell proliferation inhibition. Thus, our results indicated that lncRNA-PVT1-5 may function as a competing endogenous RNA (ceRNA) for miR-126 to promote cell proliferation by regulating the miR-126/SLC7A5 pathway, suggesting that lncRNA-PVT1-5 plays a crucial role in lung cancer progression and lncRNA-PVT1-5/miR-126/SLC7A5 regulatory network may shed light on tumorigenesis in lung cancer.     

Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis

The balance of osteoblasts and marrow adipocytes from bone marrow mesenchymal stem cells (BM-MSCs) maintains bone health. Under aging or other pathological stimuli, BM-MSCs will preferentially differentiate into marrow adipocytes and reduce osteoblasts, leading to osteoporosis. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) participates in the osteogenic differentiation of human BM-MSCs, but the mechanism by which DANCR regulates the osteogenic differentiation of human BM-MSCs has not been fully explained. We observed that DANCR and prospero homeobox 1 (PROX1) were downregulated during osteogenic differentiation of human BM-MSCs, while miR-1301-3p had an opposite trend. DANCR overexpression decreased the levels of alkaline phosphatase, RUNX2, osteocalcin, Osterix in BM-MSCs after osteogenic induction, but DANCR silencing had the opposite result. Moreover, DANCR sponged miR-1301-3p to regulate PROX1 expression. miR-1301-3p overexpression reversed the suppressive role of DANCR elevation on the osteogenic differentiation of human BM-MSCs. Also, PROX1 elevation abolished the promoting role of miR-1301-3p overexpression on the osteogenic differentiation of human BM-MSCs. In conclusion, DANCR suppressed the osteogenic differentiation of human BM-MSCs through the miR-1301-3p/PROX1 axis, offering a novel mechanism by which DANCR is responsible for the osteogenic differentiation of human BM-MSCs.

     

Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis

The hepatitis B virus core protein (HBc), also named core antigen, is well-known for its key role in viral capsid formation and virus replication. Recently, studies showed that HBc has the potential to control cell biology activity by regulating host gene expression. Here, we utilized miRNA microarray to identify 24 upregulated miRNAs and 21 downregulated miRNAs in HBc-expressed HCC cells, which were involved in multiple biological processes, including cell motility. Consistently, the in vitro transwell assay and the in vivo tail-vein injection model showed HBc promotion on HCC metastasis. Further, the miRNA-target gene network analysis displayed that the deleted in liver cancer (DLC-1) gene, an important negative regulator for cell motility, was potentially targeted by several differentially expressed miRNAs in HBc-introduced cells. Introduction of miRNAs mimics or inhibitors and 3′UTR luciferase activity assay proved that miR-382-5p efficiently suppressed DLC-1 expression and its 3′-UTR luciferase reporter activity. Importantly, cotransfection of miR-382-5p mimics/inhibitors and the DLC-1 expression vector almost abrogated HBc promotion on cell motility, indicating that the miR-382-5p/DLC-1 axis is important for mediating HBc-enhanced HCC motility. Clinical HCC samples also showed a negative correlation between miR-382-5p and DLC-1 expression level. Furthermore, HBc-positive HCC tissues showed high miR-382-5p level and reduced DLC-1 expression. In conclusion, our findings revealed that HBc promoted HCC motility by regulating the miR-382-5p/DLC-1 axis, which might provide a novel target for clinical diagnosis and treatment.     

Long non-coding RNA BACE1-AS plays an oncogenic role in hepatocellular carcinoma cells through miR-214-3p/APLN axis

BACE1 antisense RNA (BACE1-AS) is implicated in promoting cell proliferation in different types of tumors.However,the function and mechanism of BACE1-AS in hepa...     

Long non-coding RNA PRNCR1 promotes ovarian cancer cell proliferation,migration and invasion by targeting the miR-653-5p/ELF2 axis

Molecular and Cellular Biochemistry - Recent studies have shown that prostate cancer-associated long non-coding RNA, PRNCR1, plays crucial roles in the development of multiple human cancers....     

Long non-coding RNA GAS5 sensitizes renal cell carcinoma to sorafenib via miR-21/SOX5 pathway

Although the use of sorafenib appears to increase the survival rate of renal cell carcinoma (RCC) patients, there is also a proportion of patients who exhibit a poor primary response to sorafenib treatment. Therefore, it is critical to elucidate the mechanisms underlying sorafenib resistance and find representative biomarkers for sorafenib treatment in RCC patients. Herein, we identified that a long noncoding RNA GAS5 was downregulated in sorafenib nonresponsive RCCs. GAS5 overexpression conferred sorafenib sensitive to nonresponsive RCC cells, whereas knockdown of GAS5 promoted responsive RCC cells resistant to sorafenib treatment in vitro and in vivo. Mechanistically, GAS5 functioned as competing endogenous RNA to repress miR-21, which controlled its down-stream target SOX5. We proposed that GAS5 was responsible for sorafenib resistance in RCC cells and GAS5 exerted its function through the miR-21/ SOX5 axis. Our findings suggested that GAS5 downregulation may be a new marker of poor response to sorafenib and GAS5 could be a potential therapeutic target for sorafenib treatment in RCC.     

Long non-coding RNA CCAT1 promotes cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis

Cervical cancer is a serious threat to women’s health and is the third most common malignancy in women worldwide. Recent studies indicate that the long non-coding RNA CCAT1 plays a role in the malignant behavior of many tumors. However, the role of CCAT1 in cervical cancer is still unknown. Our aim is to evaluate the expression and investigate the regulatory role and potential mechanism of CCAT1 in cervical cancer. CCAT1 expression was measured by qRT-PCR. In addition, CCK-8 assays, colony formation assays, qRT-PCR assays, Transwell assays and xenograft experiments were performed to determine the role of CCAT1 in the proliferation and invasion in cervical cancer cells. The expression of CCAT1 in the cervical cancer tissues was higher than in the adjacent normal tissues. Overexpressing CCAT1 promoted cervical cancer cell proliferation, colony formation, and invasion in vitro. Elevated CCAT1 suppressed miR-181a expression, which was accompanied by an increased expression of MMP14 and HB-EGF. In contrast, knocking down CCAT1 resulted in increased expression of miR-181a, along with decreased expression of MMP14 and HB-EGF. Thus, CCAT1 is a key oncogenic lncRNA associated with cervical cancer and plays a role in promoting cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis.     

Long non-coding RNA SNHG1/microRNA-195-5p/Yes-associated protein axis affects the proliferation and metastasis of gastric cancer via the Hippo signaling pathway

Functional & Integrative Genomics - Long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been found to be highly expressed in gastric cancer (GC). However, the study for...     

Long non-coding RNA SNHG14 aggravates LPS-induced acute kidney injury through regulating miR-495-3p/HIPK1

Acute kidney injury(AKI)is a complex syndrome with an abrupt decrease of kidney function,which is associated with high morbidity and mortality.Sepsis is the com...     

Long non-coding RNA PVT1 promotes malignancy in human endometrial carcinoma cells through negative regulation of miR-195-5p

The plasmacytoma variant translocation 1 (PVT1)¹ gene is a long non-coding RNA (lncRNA)² that has been shown to be an oncogene in many cancers. Herein, the function and potential molecular mechanisms connecting PVT1 and miR-195-5p were elucidated in endometrial cancer cell lines. Quantitative real-time PCR and fluorescence in situ hybridization (FISH)³ demonstrated that PVT1 is up-regulated concomitant with miR-195-5p down-regulation in human endometrial carcinoma tissues. PVT1 knockdown inhibited cell proliferation, migration, and invasion while facilitating apoptosis of endometrial cancer cells. Moreover, restoration of miR-195-5p due to PVT1 knockdown exerted tumor-suppressive functions. We observed that PVT1 promotes malignant cell behavior by decreasing miR-195-5p expression. Binding of PVT1 and miR-195-5p was confirmed using luciferase assays. Furthermore, expression of miR-195-5p negatively correlates with PVT1 expression. At the molecular level, either PVT1 knockdown or miR-195-5p overexpression resulted in a decrease of acidic fibroblast growth factor receptor (FGFR1)⁴ and basic fibroblast growth factor (FGF2).⁵ FGFR1 and FGF2 are targets of miR-195-5p that play a critical role in endometrial carcinoma by activating PI3K/AKT and MAPK/Erk pathways. Remarkably, PVT1 knockdown combined with miR-195-5p overexpression led to tumor regression in vivo. Overall, these results depict a novel pathway mediated by PVT1 in endometrial carcinoma, which may have potential application for endometrial carcinoma therapy.     

Long non-coding RNA HOXA-AS3 facilitates the malignancy in colorectal cancer by miR-4319/SPNS2 axis

Journal of Physiology and Biochemistry - Growing evidence has shown the oncogenic role of long non-coding RNA HOXA-AS3 in the progression of several types of cancers, while the effect of HOXA-AS3...     

Long non-coding RNA ZFAS1 exerts a protective role to alleviate oxygen and glucose deprivation-mediated injury in ischemic stroke cell model through targeting miR-186-5p/MCL1 axis

Cytotechnology - In recent years, accumulating articles have revealed that long non-coding RNAs (lncRNAs) play crucial roles in ischemic stroke (IS). A previous study found that lncRNA zinc finger...     

Long noncoding HOXA11-AS knockdown suppresses the progression of non-small cell lung cancer by regulating miR-3619-5p/SALL4 axis

Journal of Molecular Histology - Accumulating evidence suggested that many long noncoding RNAs (lncRNAs) were widely involved in the development and progression of non-small cell lung cancer...     

Circular RNA has_circ_0000034 accelerates retinoblastoma advancement through the miR-361-3p/ADAM19 axis

Molecular and Cellular Biochemistry - Retinoblastoma (RB) is an intraocular malignancy that mainly occurs in infants and young children under 5 years of age. Circular RNA hsa_circ_0000034...     

RETRACTED ARTICLE: Resibufogenin suppresses tumor growth and Warburg effect through regulating miR-143-3p/HK2 axis in breast cancer

Molecular and Cellular Biochemistry - MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the...