Down-regulation of the global regulator SATB1 by statins in COLO205 colon cancer cells

Special AT-rich sequence binding protein 1 (SATB1) regulates the expression of more than 1,000 genes in tumor cells. SATB1 expression has been implicated in metastasis, and its silencing results in reduced cancer progression and the reversion of metastatic cells to normal appearance. Therefore, any compound causing down-regulation of SATB1 expression or activity may be exploited for its therapeutic potential in terms of cancer regression. Earlier studies showed that the 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (statin drugs), which are widely used to treat hypercholesterolemia, possess other pleotropic activities. These are now increasingly gaining attention for their cancer prevention abilities. However, the downstream interplay of the molecular mechanisms of such anti-cancer activities is unclear. Here, we show that SATB1 is down-regulated by statins in a time- and dose-dependent manner in COLO205 cells. This effect was statin-specific as the down-regulation of SATB1 was brought about by hydrophobic statins, such as simvastatin and fluvastatin, but not by hydrophilic pravastatin. Notably, treatment with mevalonate, an intermediate in the cholesterol and isoprenoid biosynthetic pathways, led to the inhibition of SATB1 down-regulation and cytotoxicity mediated by statins. Treatment with the proteasome inhibitors lactacystine and MG-132 inhibited the statin-mediated down-regulation of SATB1, suggesting that regulation occurs at the post-translational level. Thus, our results demonstrate a novel molecular mechanism for the anti-cancer activity of statin drugs in colon cancer cells, without invoking significant cytotoxicity

Molecular characterization of ageratum enation virus and beta satellite associated with leaf curl disease of fenugreek in India

Cisplatn is one of the chemotherapy for the treatment of triple‐negatve breast cancer (TNBC), but its effectveness is limited because of the phenomenon of chemoresistance. miR‐638 was shown to regulate chemoresistance; however, it has never been validated in the cisplatn‐resistant tumor from patents. This present study aimed to identfy the key gene regulatory networks of miR‐638 and evaluate the potental role of the miR‐638 and its targets as potental prognosis biomarkers for cisplatn‐resistance triple‐negatve breast cancer patents. The miR‐638 target was obtained from the miRecords database while the mRNA of chemoresistance biomarker candidate was obtained from the GSE18864 of GEO database, which is mRNA of cisplatn‐resistance TNBC patents. CCND1 and FZD7 are potental candidates for cisplatn chemoresistance biomarkers in patents with TNBC. Moreover, a Kaplan‐Meier survival plot showed that breast cancer patents with low mRNA levels of FZD7 had signifcantly worse overall survival than those in higher mRNA expression group. Taken together, miR‐638 plays a role in cisplatn resistance mechanism through a mechanism involving its target gene CCND1 and FZD7. Overall, miR‐638, CCND1, and FZD7 are candidates for cisplatn biomarker resistance in TNBC

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Not AvailableOkra samples showing yellow vein mosaic, vein twisting and bushy appearance were collected from different locations of India during the surveys conducted between years 2005–2009. The dot blot and PCR detection revealed that 75.14% of the samples were associated with monopartite begomovirus and remaining samples with bipartite virus. Whitefly transmission was established for three samples representing widely separated geographical locations which are negative to betasatellites and associated with DNA-B. Genome components of these three representative isolates were cloned and sequenced. The analysis of DNA-A-like sequence revealed that three begomovirus isolates shared more than 93% nucleotide sequence identity with bhendi yellow vein mosaic virus from India (BYVMV), a monopartite begomovirus species that was reported previously as causative agent of bhendi yellow mosaic disease in association of bhendi yellow vein mosaic betasatellite. Further, the DNA-B-like sequences associated with the three virus isolates shared no more than 90% sequence identity with tomato leaf curl New Delhi virus (ToLCNDV). Analyses of putative iteron-binding sequence required for trans-replication suggests that begomovirus sequences shared compatible rep-binding iterons with DNA-B of ToLCNDV. Our data suggest that the monopartite begomovirus associated with okra yellow vein disease has captured DNA-B of ToLCNDV to infect okra. Widespread distribution of the complex shows the increasing trend of the capturing of DNA-B of ToLCNDV by monopartite begomoviruses in the Indian subcontinent. The recombination analysis showed that the DNA-A might have been derived from the inter-specific recombination of begomoviruses, while DNA-B was derived from the ToLCNDV infecting different hosts.Not Availabl

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Not AvailableLeaves from French bean plants with severe leaf curl (ten samples) and from asymptomatic plants from 10 felds (FB1–10) in the Western Ghat region of Karnataka, India were collected. Virus isolate FB01 from French bean was shown to be transmitted by whitefy Bemisia tabaci cryptic species Asia I. DNA was isolated from the samples (ten feld samples and one sample infected with FB01 via whitefy) and subjected to PCR to confrm begomovirus infection using specifc primers. All 11 were positive for the expected 1.2-kb amplicon. The sequence analysis of the 1.2-kb amplicon showed that all isolates shared more than 98% nucleotide identity. Further, the complete genome from isolate FB01 was amplifed and sequenced and shown to share a maximum nucleotide identity (89.3%) with Ageratum yellow vein Sri Lanka virus. As per the ICTV species threshold for begomoviruses, the virus is considered as a new species, with the proposed name French bean leaf curl virus (FbLCV). The samples were subjected to PCR using specifc primers for DNA B, betasatellite and alphasatellite; only betasatellites were amplifed. The detected betasatellite shared maximum nucleotide identity (92.6%) with Synedrella yellow vein betasatellite. Recombination analysis indicated that FbLCV and betasatellite were recombinants. The signifcance of these fndings are discussed.Indian Council of Agricultural Researc

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Not AvailableThe calendula plants showing the yellow vein disease symptoms were collected from Madikeri dist. of Karnataka state, India. Total nucleic acid isolated from the infected Calendula plant leaf samples were subjected to PCR using begomovirus specific primer. The PCR diagnostic and whole genome sequencing indicated that the symptomatic calendula plants are associated with Papaya leaf curl virus (PaLCuV). The viral complete genome causing yellow vein disease had showed maximum nucleotide (nt) identity of 91.5–94.9% with begomovirus (PaLCuV) strains previously identified begomovirus from India infecting Croton bonplandianum, Acalypha sp. and chilli. Regarding to begomoviruses criteria for strain demarcation (91% nucleotide similarity), the virus infecting calendula in this report is considered as a strain of PaLCuV. The betasatellite showed maximum nucleotide identity of 89.8% with croton yellow vein mosaic betasatellite (CroYVMB) infecting okra and Croton. According to our knowledge, this is the first report of PaLCuV infecting the Calendula, in India. The result also indicated that calendula plants infected with PaLCuV may act as an alternate host for other economically important plant pathogens.Indian Council of Agricultural Researc

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Not AvailableA begomovirus isolate (OY136A) collected from okra plants showing upward leaf curling, vein clearing, vein thickening and yellowing symptoms from Bangalore rural district, Karnataka, India was characterized. The sequence comparisons revealed that, this virus isolate share highest nucleotide identity with isolates of Cotton leaf curl Bangalore virus (CLCuBV) (AY705380) (92.8 %) and Okra enation leaf curl virus (81.1–86.2 %). This is well supported by phylogentic analysis showing, close clustering of the virus isolate with CLCuBV. With this data, based on the current taxonomic criteria for the genus Begomovirus, the present virus isolate is classified as a new strain of CLCuBV, for which CLCuBV-[India: Bangalore: okra: 2006] additional descriptor is proposed. The betasatellite (KC608158) associated with the virus is having more than 95 % sequence similarity with the cotton leaf curl betasatellites (CLCuB) available in the Gen- Bank.The recombination analysis suggested, emergence of this new strain of okra infecting begomovirus might have been from the exchange of genetic material between BYVMV and CLCuMuV. The virus was successfully transmitted by whitefly and grafting. The host range of the virus was shown to be very narrow and limited to two species in the family Malvaceae, okra (Abelmoschus esculentus) and hollyhock (Althaea rosea), and four in the family Solanaceae.Not Availabl

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Not AvailableTomato plants showing witches broom symptoms were collected from different states of India. The presence of phytoplasma infection was confirmed by PCR using phytoplasma-specific primer of 16S rRNA and SecY gene. The sequence analysis of 16S rRNA and SecY gene of eight tomato big bud phytoplasmas showed maximum nucleotide (nt) identity of 95 - 100% with Peanut WB group (16SrII). Further in-silico RFLP analysis of 16S rRNA gene of TBB-Pun1, TBB-Ban, TBB-mal, TBB-Guj and TBB-Vns showed similarity coefficient of 0.68–0.95. Since threshold similarity coefficient for classifying the phytoplasma into new subgroup is set at 0.97, the strain under study significantly distinct from the representative strains in the subgroups of pea nut witches broom. Further, the phylogenetic analysis of tomato big bud phytoplasmas revealed that, they are closely clustered with peanut witches’- broom strains (16Sr II), specifically within the 16Sr II-D and 16Sr II-A subgroups. A comprehensive recombination analysis showed the evidence of both intra and inter-species recombination in seven tomato big bud isolates with most part of their 16Sr RNA F2nR2 fragments descending from Ca.P.brasiliense (16Sr XV) as major parent, except isolate TBB-Vns which had an intra species recombination with Cactus witches-broom-16Sr II-L as major parent. Similarly, in case of SecY gene, all the seven isolates have intra-species recombination with major portion descending from Vinca virescence - [16Sr VI - A] and Potato purple top wilt - [16Sr XVIII - B]. The genetic similarities and the potential threat of this new phytoplasma belonging to 16Sr II group of Peanut witches’ broom’ group infecting tomato in India are discussed.Not Availabl

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Not AvailableTomato is widely grown vegetable crop in India and viral diseases are major constraint for its production in the country. The chilli leaf curl virus (ChiLCV) infecting chilli reported from the Indian subcontinent is found associated with tomato enation leaf curl disease in tomato growing areas of India. The leaf samples showing enation leaf curl symptoms were collected from tomato fields located in Sonipet (ten infected and one healthy sample) of Haryana state and Varanasi (five infected and one healthy sample) of Uttar Pradesh state, India. Full length genome of begomovirus and associated betasatellite were amplified, cloned and sequenced. The Viral sequences represented in the begomovirus clones showed 89–100 % nucleotide sequence identity, suggesting that they represent a single species. Comparisons to sequences available in the databases showed nucleotide sequence identities of 87.3–91.8 % for TC-Vns and 87.8–98.4 % for TC287 and TC290, with Indian isolates of ChiLCV. The betasatellite sequences obtained had 83.1–94.1 % identity with tomato leaf curl Bangladesh betasatellite (ToLCBDB). An analysis for recombinant origin of genome and betasatellite showed major part of their genome was likely to be originated by recombination of begomo viruses infecting different host species resulting in evolution of new recombinant virus. The ChiLCV-tom reported in the current study is another distinct strain of ChiLCV identified in tomato causing enation leaf curl disease in India. The significance of these findings is discussed.Not Availabl

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Not AvailableThe leaf sample from okra plants showing prominent yellow vein mosaic symptoms and healthy plant without any virus symptoms were collected from farmer’s field. The presence of begomovirus in the infected sample was confirmed by polymerase chain reaction (PCR) and the amplicons were cloned and sequenced. The genome analysis showed that the isolate in the present study had 99% nucleotide identity with Bhendi yellow vein mosaic virus (BYVMV) revealing it as BYVMV variant. The genetic species of Bemisia tabaci collected from fields were identified as Asia-1 and MEAM-1 genetic species based on silver leaf assay, sequence characterized amplified region marker, and mtCOI gene sequence. The comparative virus– vector relationship of both genetic species of B. tabaci indicates a minimum of two and three B. tabaci in MEAM- 1 and Asia-1 genetic species, respectively, per plant were required to transmit the disease. The minimum acquisition access period and inoculation access period of 15 (MEAM- 1) and 20 min (Asia-1) were required to transmit the YVMD; it was further confirmed by nucleic acid hybridization using coat protein gene-specific probe of BYVMV. With respect to the sex, the female B. tabaci were more efficient in transmitting the disease as compared to male ones in both the genetic species of B. tabaci. The MEAM-1 to transmit the BYVMV more efficiently than Asia-1 genetic species of B. tabaci.Not Availabl

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Not AvailableTotal twenty five snake gourd leaf samples showing severe mosaic symptoms were collected from different farmer’s field in Varanasi, Uttar Pradesh State of India. The partial amplified PCR products (1.2kb fragment) were cloned and sequence characterized. On the basis of the determined sequences and sequence analysis, begomovirus associated with symptoms in majority of samples (20) was found to be a member of a bipartite begomovirus species which is closely related to Tomato leaf curl New Delhi virus (ToLCNDV). Therefore one sample was selected for full-length amplification using RCA method. SDT analysis of complete genome of the begomovirus (SnG-1) showed highest nucleotide (nt) identity of 88.5-96.3% (DNA-A) and 82.7-93.3% (DNA-B) with Tomato leaf curl New Delhi virus (ToLCNDV) infecting different cucurbits in Indian subcontinent. An analysis for recombinant origin of genomes (DNA-A and DNA-B-like sequence) showed major part of their genome was likely, originated by recombination of previously reported begomoviruses (ToLCNDV, ToLCPaV and SLCCNV) infecting different cucurbits species resulting in evolution of new recombinant virus. This is the first report of ToLCNDV associated Snake gourd India and significance of these findings is discussed.Not Availabl