CRNDE Contributes Cervical Cancer Progression by Regulating miR-4262/ZEB1 Axis.

BACKGROUND: Cervical cancer is a lethal gynecologic cancer in women. Long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was recognized as a significant oncogene in multiple cancers. However, the functional role of CRNDE in cervical cancer remains poorly explored. METHODS: The expression of CRNDE, microRNA-4262 (miR-4262) and zinc-finger E-box binding homeobox 1 (ZEB1) in cervical cancer tumors and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Colony formation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) were performed to detect cell viability. Flow cytometry and caspase-3 activity assay were conducted to evaluate cell apoptosis. The interaction between miR-4262 and CRNDE or ZEB1 was verified by dual-luciferase reporter system. Transwell assay was employed to evaluate cell migration and invasion. The relative protein expression was assessed by Western blot. RESULTS: CRNDE and ZEB1 were up-regulated, while miR-4262 was down-regulated in cervical cancer tissues and cells. We found that CRNDE sponged miR-4262 and ZEB1 was a target of miR-4262. In addition, miR-4262 inhibitor abolished CRNDE silencing-induced repression on cell proliferation, EMT, migration, invasion and promotion on cell apoptosis. Furthermore, ZEB1 rescued the effects of miR-4262 overexpression or CRNDE deletion on cervical cancer progression. Our data showed that CRNDE targeted miR-4262 to regulate ZEB1 expression in cervical cancer cells. Besides, CRNDE expedited cervical cancer progression through wnt/ß-catenin pathway via sponging miR-4262 and altering ZEB1 expression. CONCLUSION: Our findings demonstrated that CRNDE facilitated the progression of cervical cancer through activation of wnt/ß-catenin pathway by regulating miR-4262/ZEB1 axis, representing a prospective targeted therapy for cervical cancer.

Circular RNA MTO1 Inhibits the Proliferation and Invasion of Ovarian Cancer Cells Through the miR-182-5p/KLF15 Axis.

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs and have been shown to play important roles in a variety of physiological processes. Recently, dysregulation of circRNAs has been identified in many types of cancers. In this study, we analyzed the expression profile and biological functions of circMTO1 in ovarian cancer. We demonstrated that circMTO1 was downregulated in ovarian cancer tissues and cell lines. Upregulation of circMTO1 inhibited proliferation and invasion of ovarian cancer cells while downregulation of circMTO1 promoted these processes. Mechanistically, we showed that circMTO1 sponged miR-182-5p to support KLF15 expression, eventually leading to inhibition of ovarian cancer progression. In conclusion, our study suggested circMTO1 as a novel biomarker and therapeutic target for ovarian cancer treatment.

miR-125a-5p post-transcriptionally suppresses GALNT7 to inhibit proliferation and invasion in cervical cancer cells via the EGFR/PI3K/AKT pathway.

BACKGROUND: The carcinogenesis and progression of cervical cancer is a complex process in which numerous microRNAs are involved. The purpose of this study is to investigate the role of miR-125a-5p in progression of cervical cancer. METHODS: RT-qPCR was used to detect the expression of miR-125a-5p and GALNT7 in cervical cancer tissues and cell lines. Then, the miR-125a-5p mimic, miR-125a-5p inhibitor, GALNT7 siRNA, or/and pcDNA-GALNT7 were respectively transfected into HeLa and Caski cervical cancer cells, and Cell Counting kit-8 assay, Transwell assay and flow cytometry analysis were respectively used to observe cell proliferation, invasion and apoptosis. Subsequently, luciferase reporter gene assay was employed in confirming the target relationship between miR-125a-5p and GALNT7. MiR-125a-5p mimic or/and pcDNA-GALNT7 were transfected into the cervical cancer cells at the absence of epidermal growth factor (EGF) or not, and the pcDNA-GALNT7 was transfected into the cervical cancer cells at the absence of inhibitors of multiple kinases or not. Furthermore, the effect of miR-125a-5p on tumor growth was also studied using a xenograft model of nude mice. RESULTS: MiR-125a-5p was down-regulated in both cervical cancer tissues and cell lines and it inhibited cell proliferation and invasion of cervical cancer cells. MiR-125a-5p directly targeted and post-transcriptionally downregulated GALNT7 that was strongly upregulated in cervical cancer tissues and cell lines. Similar to the effect of miR-125a-5p mimic, silencing GALNT7 inhibited proliferation and invasion of cervical cancer cells. In addition, miR-125a-5p overexpression could counteract both GALNT7- and EGF-induced cell proliferation and invasion. GALNT7 promoted cell proliferation and invasion by activating the EGFR/PI3K/AKT kinase pathway, which could be abated by the inhibitors of the kinases. Moreover, the role of miR-125a-5p inhibited tumor formation in cervical cancer by suppressing the expression of GALNT7 in vivo. CONCLUSION: In conclusion, miR-125a-5p suppressed cervical cancer progression by post-transcriptionally downregulating GALNT7 and inactivating the EGFR/PI3K/AKT pathway.

Asiatic acid exerts anticancer potential in human ovarian cancer cells via suppression of PI3K/Akt/mTOR signalling.

Context Asiatic acid, a triterpenoid compound extracted from the tropical medicinal plant Centella asiatica (Family: Apiaceae), has exhibited various biological activities. Objective This study was performed to investigate the cytotoxic effects of asiatic acid on human ovarian cancer cells. Materials and methods SKOV3 and OVCAR-3 ovarian cancer cells were exposed to different concentrations of asiatic acid (10-100 µg/mL) for 72 or 48 h. Cell viability, colony formation, cell cycle distribution, apoptotic response were examined. Involvement of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was tested. Results At the concentration of 40 µg/mL, asiatic acid caused about 50% reduction in the viability of ovarian cancer cells, but had little effect on the viability of normal human ovarian epithelial cells. Asiatic acid at 10 µg/mL reduced colony formation of ovarian cancer cells by 25-30%. Asiatic acid-treated cells showed a cell cycle arrest at the G0/G1 phase and 7- to 10-fold increase in apoptosis. The phosphorylation levels of PI3K, Akt and mTOR were remarkably lower in asiatic acid-treated cells. Overexpression of constitutively active Akt partially reversed the cytotoxic effects of asiatic acid, as evidenced by increased cell viability and colony formation. Furthermore, knockdown of Akt mimicked the growth-suppressive activity of asiatic acid. Discussion and conclusion These results provide first the evidence for the anticancer potential of asiatic acid in ovarian cancer cells, partially via inactivation of the PI3K/Akt/mTOR pathway. Asiatic acid may represent a potential therapeutic agent for ovarian cancer.