Linc00887 suppresses tumorigenesis of cervical cancer through regulating the miR-454-3p/FRMD6-Hippo axis.

BACKGROUND: Emerging evidence suggested that long intergenic noncoding RNA (lincRNA) 00887 (NR_024480) reduced the invasion and metastasis of non-small cell lung cancer by sponging miRNAs degradation. However, the role and regulatory mechanism of linc00887 in the progression of cervical cancer remain largely unknown. METHODS: In vivo or vitro, RT-qPCR assay was used to detect the expression of linc00887 in human normal (N = 30), cervical cancer tissues (N = 30), human normal cervical epithelial cells (Ect1/E6E7) and cervical cancer cell lines (HeLa, C33A). Then, CCK-8 and Transwell assays were used to examine cell proliferation and invasion when linc00887 was overexpressed or knocked down. In addition, bioinformatics, luciferase reporter gene and pull-down assays were used to predict and validate the relationship between linc00887 and miR-454-3p. Moreover, we detected the expression of miR-454-3p in Ect1/E6E7, HeLa and C33A cells when linc00887 was overexpressed or knocked down. Cell proliferation and invasion were also measured when pcDNA-linc00887 and miR-454-3p were transfected alone or together. Next, miR-454-3p target gene was predicted and validated by bioinformatics and luciferase reporter gene assays. Gain- and loss-of-function experiments were performed in HeLa cells to evaluate the effect of miR-454-3p or linc00887 on the expression of FERM domain containing protein 6 (FRMD6) protein and several key proteins in the FRMD6-Hippo signaling pathway. RESULTS: Linc00887 was downregulated in cervical cancer tissues or human cervical cancer cell lines (Hela, C33A) compared with normal tissues or cell lines. Overexpression of linc00887 inhibited proliferation and invasion HeLa and C33A cells, while linc00887 knockdown had the opposite effect. Linc00887 bound with miR-454-3p, and overexpression of miR-454-3p rescued linc00887-induced inhibition proliferation and invasion of HeLa cells. MiR-454-3p targeted and suppressed the expression of FRMD6, and linc00887 suppressed tumorigenesis of cervical cancer through activating the FRMD6-Hippo signaling pathway. CONCLUSIONS: Linc00887, sponging miR-454-3p, inhibited the progression of cervical cancer by activating the FRMD6-Hippo signaling pathway.

MLAA-34 knockdown shows enhanced antitumor activity via JAK2/STAT3 signaling pathway in acute monocytic leukemia.

MLAA-34 is a novel leukemia-associated gene closely related to the carcinogenesis of acute monocytic leukemia (AML). MLAA-34 over expression has been observed to inhibit apoptosis in vitro. JAK2/STAT3 pathway plays an important role in cell proliferation, differentiation and inhibition of apoptosis in number of cancers. However, the relationship and interaction between MLAA-34 and JAK2/STAT3 has never been investigated in AML. This study investigates and reports a novel relationship between MLAA-34 and JAK2/STAT3 pathway in AML both in vitro and in vivo. We constructed MLAA-34 knockdown vector and transfected U937 cells to observe its apoptotic activities in relation to JAK2/STAT3 signaling pathway in vitro and then in vivo in mouse model. Levels of expression of MLAA-34 and JAK2/STAT3 and its downstream targets were also measured in AML patients and a few volunteers. We found that MLAA-34 knockdown increased U937 apoptosis in vitro and inhibited tumor growth in vivo. Components of the canonical JAK2/STAT3 pathway or its downstream targets, including c-myc, bcl-2, Bax, and caspase-3, were shown to be involved in the carcinogenesis of AML. We also found that the JAK2/STAT3 pathway positively regulated MLAA-34 expression. We additionally identified a STAT3 binding site in the MLAA-34 promoter where STAT3 binds directly and activates MLAA-34 expression. In addition, MLAA-34 was found to form a complex with JAK2 and was enhanced by JAK2 activation. Correlation of MLAA-34 and JAK2/STAT3 was further confirmed in AML patients. In conclusion, MLAA-34 is a novel regulator for JAK2/STAT3 signaling, and in turn, is regulated by this interaction in a positive feedback loop. Thus we report a novel model of interaction mechanism between MLAA-34 and JAK2/STAT3 which can be utilized as a potential target for a novel therapeutic approach in AML.

ß-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund's adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway.

Rheumatoid arthritis (RA), autoimmune disease that is categorized via chronic inflammation manifestation, obesity, cardiovascular risk and even enhanced the mortality and affect the 0.3 and 1% of population worldwide. The current experimental study was scrutinize the anti-arthritic effect of ß-sitosterol loaded solid lipid nanoparticles (SLN) against complete Fruend adjuvant (CFA)-induced arthritis via dual pathway. Double emulsion solvent displacement method was used for the preparation of ß-sitosterol solid lipid nanoparticles (SLN). CFA was used to induce arthritis and rats were divided into different groups for 28 days. Biochemical, anti-inflammatory, pro-inflammatory cytokines and inflammatory mediator were estimated, respectively. Receptor activator of nuclear factor kappa-B ligand (RANKL), signal transducer and activator of transcription-3 (STAT3) nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1(HO-1) and Nuclear factor-κB (NF-κB) expression were estimated. ß-sitosterol-SLN significantly (p < .001) reduced the paw edema, arthritic index and increased the body weight. ß-sitosterol-SLN increased the redox status of synovium {reduce the malonaldehyde (MDA) and increase superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT)} level and reduced the cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2, interleukin-6, interleukin-16, interleukin-17 and increased level of interleukin-10, Transforming growth factor beta (TGF-ß). ß-sitosterol-SLN significantly (p < .001) reduced the level of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), vascular Endothelial Growth Factor (VEGF) and NF-κB. ß-sitosterol-SLN significantly increased the expression of HO-1,Nrf2 and decreased the expression of NF-κB, RANKL, STAT3. In conclusion, ß-sitosterol SLN showed the antiarthritic effect via suppression of NF-kB and activation of HO-1/Nrf-2 pathway.

Knockdown of circular RNA UBAP2 inhibits the malignant behaviours of esophageal squamous cell carcinoma by microRNA-422a/Rab10 axis.

Esophageal squamous cell carcinoma (ESCC) is a major type of esophageal cancer, accounting for about 90% of cases. Circular RNA UBAP2 (circUBAP2) is involved in the progression of several types of cancers. However, the role of circUBAP2 in ESCC remains unclear. In the present study, circUBAP2 expression was found to be upregulated in ESCC tumour tissues. Knockdown of circUBAP2 through infection with lentiviral vector encoding shRNA targeting circUBAP2 (sh-circUBAP2) inhibited the proliferation, migration and invasion of ESCC cells. In addition, circUBAP2 significantly promoted the proliferation, migration and invasion of ESCC cells. In vivo xenograft assay demonstrated that circUBAP2 downregulation suppressed the tumour growth of ESCC. Further mechanism investigations proved that circUBAP2 exerted its role via sponging microRNA (miR)-422a, and miR-422a directly targeted Rab10 in ESCC cells. These findings suggested that circUBAP2 acted as oncogene through regulating the miR-422a/Rab10 axis in ESCC.

The significance of the morphological and immunological characteristics in the diagnosis of parotid mammary analogue secretory carcinoma: five case reports and a review of the literature.

Mammary analogue secretory carcinoma (MASC) of the salivary glands is rarely reported. In this article, the histopathological features of 5 cases of parotid MASC were retrospectively analyzed. AB/PAS and immunohistochemical staining of S-100, mammaglobin and P63 was performed, which were validated by the ETV6-fluorescent FISH detection of NTRK3 gene. The tumors were composed of two kinds of tumor cells. One kind of cells was rich in cytoplasms, transparent or vacuole-like, partial basophilic double tropism, but another type of cellular cytoplasm was acidophilic. The karyotype was consistent between two types of tumors in the vacuolar pattern. Although the tumor cells were arranged in different forms, the cystic (capsule or microcapsule) structures were constantly observed. Two kinds of tumor cells produced different secretions, which were distributed among the tumor cells. Tumor tissues were divided by hardened collagen interstitial, even in the infiltration lesion, collagen and tumor cells mass was also inseparable. The expression of mammaglobin and S-100 significantly differed between the two types of tumor cells. These characteristics contribute to the differential diagnosis of MASC. ETV6-NTRK3 gene detection can be applied in the diagnosis of atypical cases, but it should not be done routinely.