Long noncoding RNA POU3F3 promotes cancer cell proliferation in prostate carcinoma by upregulating rho-associated protein kinase 1

Long noncoding RNAs (lncRNAs) POU3F3 is overexpressed in esophageal squamous-cell carcinomas, while its role in other human cancers is unclear. In this study we found that POU3F3 and rho-associated protein kinase 1 (ROCK1) were both increased in tumor tissues than in adjacent healthy tissues of patients with prostate carcinoma. Expression levels of POU3F3 increased with increase in the diameter of tumor but were not significantly affected by lymph node metastasis or distant metastasis. Expression levels of POU3F3 and ROCK1 were positive correlated in tumor tissues but not in adjacent healthy tissues. POU3F3 and ROCK1 overexpression promoted, while ROCK1 knockdown inhibited the proliferation of prostate carcinoma cells. ROCK1 knockdown reduced the enhancing effect of POU3F3 overexpression on cancer cell proliferation. POU3F3 overexpression led to ROCK1 overexpression in prostate carcinoma cells, while ROCK1 overexpression did not significantly affect POU3F3 expression. Therefore, lncRNA POU3F3 may promote cancer cell proliferation in prostate carcinoma by upregulating ROCK1.     

Apolipoprotein C1 promotes prostate cancer cell proliferation in vitro

Here, we aimed to investigate the carcinogenic effects of apolipoprotein C1 (APOC1) in prostate cancer (PCa). APOC1 expression was evaluated in PCa and normal prostate specimens, and lentivirus‐mediated RNA interference was used to knockdown APOC1 in DU145 cells. The effects of APOC1 silencing on cell proliferation, cell cycle arrest, and apoptosis were assessed. APOC1 expression was much higher in PCa tissues than in normal tissues. Moreover, APOC1 silencing inhibited cell proliferation and colony formation, arrested cell cycle progression, and enhanced apoptosis in DU145 cells. Additionally, APOC1 silencing decreased survivin, phospho‐Rb, and p21 levels and increased cleaved caspase‐3 expression. These data supported the procarcinogenic effects of APOC1 in the pathogenesis of PCa and suggested that targeting APOC1 may have applications in the treatment of PCa.     

Long noncoding RNA CHL1-AS1 promotes cell proliferation and migration by sponging miR-6076 to regulate CHL1 expression in endometrial cancer

Endometrial cancer (EC) is deemed to be the most typical gynecologic malignant tumor. Despite the incidence of EC being lower in Asia than that in western countries, substantial increased incidence has been observed in the past few decades in Asia. Although various molecular testing methods and genomic science have developed, the overall prognosis is still disappointing. LncRNAs have been found to influence the progression of various cancers. CHL1-AS1 has been found to be upregulated in ovarian endometriosis, nevertheless, the molecular mechanism and biological function of CHL1-AS1 in EC have not been explored. In our exploration, both CHL1-AS1 and CHL1 were upregulated in EC cells. Knockdown of CHL1-AS1 or CHL1 inhibited cell proliferation and migration in EC. Furthermore, microRNA-6076 (miR-6076) could bind with CHL1-AS1 or CHL1, and regulate the expression of CHL1. Finally, absence of miR-6076 or overexpression of CHL1 can partially rescue the effect of CHL1-AS1 knockdown or miR-6076 upregulation on cell proliferation and migration, respectively. All in all, our research was the first endeavor to study the underlying mechanism of CHL1-AS1 in EC and confirmed that CHL1-AS1 regulated EC progression via targeting the miR-6076/CHL1 axis, offering new insight into treating EC.     

Upregulated KDM4B promotes prostate cancer cell proliferation by activating autophagy

Castration-resistant prostate cancer (CRPC) causes most of the deaths in patients with prostate cancer (PCa). The androgen receptor (AR) axis plays an important role in castration resistance. Emerging studies showed that the lysine demethylase KDM4B is a key molecule in AR signaling and turnover, and autophagy plays an important role in CRPC. However, little is known about whether KDM4B promotes CRPC progression by regulating autophagy. Here we used an androgen-independent LNCaP (LNCaP-AI) cell line to assay aberrant KDM4B expression using qPCR and western blot analysis and investigated the function of KDM4B in regulating cell proliferation. We found that KDM4B was markedly increased in LNCaP-AI cells compared with LNCaP cells. KDM4B level was significantly correlated with the Gleason score in PCa tissues. In vitro, KDM4B overexpression in CRPC cells promoted cell proliferation, whereas knockdown of KDM4B significantly inhibited cell proliferation. Upregulated KDM4B contributed to activate Wnt/β-catenin signaling and autophagy. Moreover, KDM4B activated autophagy by regulating the Wnt/β-catenin signaling. Finally, we demonstrated that autophagy inhibition attenuated KDM4B-induced CRPC cell proliferation. Our results provided novel insights into the function of KDM4B-driven CRPC development and indicated that KDM4B may be served as a potential target for CRPC therapy.     

miRNA-191对前列腺癌的增殖、迁移侵袭能力的影响及其机制

目的:观察miRNA-191对前列腺癌的增殖、迁移和侵袭能力的影响,并探讨其机制。方法:分别检测4种人前列癌细胞系(PC-3、DU-145、LNCa P、22RU1)及人正常前列腺细胞RWPE-2中miRNA-191的表达水平,并选择前列腺癌细胞系PC-3作为实验对象。将PC-3细胞分为3组:空白对照组(不转染)、miRNA-191 NC组(Inhibitor NC转染PC-3细胞)、miRNA-191 Inhibitor组(miRNA-191 Inhibitor转染PC-3细胞),每组设置3个复孔。采用RTq PCR法检测PC-3细胞miRNA-191和PLCD1的mRNA表达水平;采用CCK8法检测PC-3细胞增殖水平;采用划痕实验和侵袭实验分别检测PC-3细胞迁移能力和侵袭能力;通过Targetscan靶基因预测网站,筛选PLCD1作为miRNA-191的靶向蛋白,并用双荧光素酶靶标实验验证;采用Western blot法检测PC-3细胞PLCD1的蛋白表达。结果:与RWPE-2细胞相比,人前列癌细胞中mi NRA-191的表达水平显著升高(P<0.05),且miRNA-1...     

Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.     

Knockdown of long noncoding RNA urothelial carcinoma associated 1 inhibits colorectal cancer cell proliferation and promotes apoptosis via modulating autophagy

Long noncoding RNA urothelial carcinoma associated 1 (UCA1) has been implicated in the growth and metastasis of colorectal cancer (CRC), and autophagy contributes to tumorigenesis and cancer cell survival. However, the regulatory role of UCA1 in CRC cell viability by modulating autophagy remains unclear. In the present study, a significant positive correlation was observed between UCA1 and microtubule-associated protein 1 light chain 3 (LC3) levels, and the elevated UCA1 was negatively correlated with the PKB/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in 293T cells. Downregulation of UCA1 inhibited autophagy activation and cell proliferation, whereas the apoptosis was increased and the cell cycle was arrested in G2 stage. The next results showed that UCA1 was markedly upregulated in Caco-2 cells. Knockdown of UCA1 significantly decreased the LC3-II and autophagy-related gene 5 (ATG5) protein levels and resulted in an increase in p62 expression. Conversely, the autophagy activator rapamycin (RAPA) reversed the effects. Furthermore, downregulated UCA1 decreased Caco-2 cells population in the G1 phase and increased the cells number in G2 phage. The cell proliferation was inhibited, and apoptosis rate was promoted. More important, RAPA could also abrogate the changes induced by knockdown of UCA1. Collectively, these data demonstrated that downregulated UCA1 induced autophagy inhibition, resulting in suppressing cell proliferation and promoting apoptosis, which suggested that UCA1 might serve as a potential new oncogene to regulate CRC cells viability by modulating autophagy.     

Long noncoding RNA SBF2-AS1 promotes colorectal cancer proliferation and invasion by inhibiting miR-619-5p activity and facilitating HDAC3 expression

Evidence, demonstrating long noncoding RNAs (lncRNAs) as critical players in cancer, remains to increase. lncRNA SBF2-AS1 was reported to be involved in several cancers, such as hepatocellular carcinoma. However, the role of SBF2-AS1 in colorectal cancer (CRC) is unknown. We showed lncRNA SBF2-AS1 expression was growing in CRC samples, especially in advanced cases. Accordingly, SBF2-AS1 possesses higher expression in CRC cell lines than in normal cell line. Moreover, SBF2-AS1 high expression indicated a low survival rate. Functionally, SBF2-AS1 knockdown suppressed the proliferation, migration, and invasion of CRC cells. In terms of mechanism, SBF2-AS1 upregulation restrained the activity of miR-619-5p and led to overexpression of HDAC3. Importantly, downregulation of miR-619-5p or HDAC3 overexpression reversed SBF2-AS1-silencing-caused suppression on proliferation and metastasis. Summarily, our findings elucidated a crucial role of SBF2-AS1 as a miR-619-5p sponge, shedding novel light on lncRNA-related prognostics.     

Long noncoding RNA PRKCQ-AS1 promotes CRC cell proliferation and migration via modulating miR-1287-5p/YBX1 axis

Colorectal cancer (CRC) brings more than 600 000 deaths every year around the globe, making itself the third most frequently occurred carcinoma. The great progress human achieved in diagnosis and treatment of various cancers has failed to reverse this trend. Fortunately, growing evidence has implied the relationship between lncRNAs and cancer progression. Long noncoding RNA (lncRNA) PRKCQ-AS1 was heightened in CRC cells and tissues and related with dismal prognosis of CRC patients. Knockdown of PRKCQ-AS1 would induce a decrease in proliferative and migrating ability of CRC cells. Also, PRKCQ-AS1 enriched in cytoplasm of CRC cells and negatively regulated miR-1287-5p level. More important, PRKCQ-AS1 could bind to argonaute 2 and function in the RNA-induced silencing complex with miR-1287-5p. Therefore, PRKCQ-AS1 was a competing endogenous RNA for miR-1287-5p. Subsequently, it was validated that miR-1287-5p could suppress the proliferative and migratory functions in CRC. Furthermore, PRKCQ-AS1 could upregulate the mRNA and protein level of YBX1 targeted by miR-1287-5p. And YBX1 expression was elevated in CRC cells and tissues. Rescue assays in vitro and in vivo showed that overexpression of YBX1 could partly offset the effect of CRC progression induced by knocking down PRKCQ-AS1, demonstrating PRKCQ-AS1 mediating CRC progression via miR-1287-5p/YBX1 pathway.