Abetment of suicide: If any person commits suicide, whoever abets the commission of such suicide shall be punished with imprisonment of either description for a term which may extend to 10 years and shall also be liable for fine (306 IPC). 113-A of Indian Evidence Act, 1872, relates to the presumption as to abetment of suicide. The offences of dowry and abetment of suicide are cognizable, nonbailable and noncompoundable.
Restricted to Arts and Entertainment Technologies majors. Sound design for theater productions including script analysis, music underscoring, SFX and cue-based playback software. Three lecture hours a week for one semester, with lab hours as required. Arts and Entertainment Technologies 320N and 339 (Topic: Theatre Sound Design) may not both be counted. Offered on the letter-grade basis only. Prerequisite: Arts and Entertainment Technologies 305.
Restricted to Arts and Entertainment Technologies majors. Design and build interactive 2D or 3D game levels (game maps) using an industry standard tool such as Unity or Unreal. Explore the design pipeline for creating levels from concept and layout, to whiteboxing, creating and integrating environment art and sound, worldbuilding, and adding simple scripted interactions, animations, sound effects, and VFX. Examine the different design process for small indie games compared to big AAA games. Three lecture hours a week for one semester, with lab hours as required. Arts and Entertainment Technologies 334C and 339 (Topic: Level Design) may not both be counted. Offered on the letter-grade basis only. Prerequisite: Arts and Entertainment Technologies 310 and 318C.
Restricted to Arts and Entertainment Technologies majors. Introduction to scripting interactive content for games using an industry-standard scripting language and game engine. Three lecture hours a week for one semester, with lab hours as required. Offered on the letter-grade basis only. Prerequisite: Arts and Entertainment Technologies 310 and 318C.
Restricted to Arts and Entertainment Technologies majors. Advanced scripting of interactive content for video games using an industry-standard scripting language and game engine. Three lecture hours a week for one semester, with lab hours as required. Offered on the letter-grade basis only. Prerequisite: Arts and Entertainment Technologies 334F.
In recent years, a large body of evidence has revealed that deregulatedmicroRNAs (miRNAs) play important roles in cancer. MiRNAs belong to a classof endogenous non-coding small RNAs that regulate gene expressionpost-transcriptionally. They bind to the 3' untranslated region (UTR) oftarget messenger RNAs (mRNAs) to promote mRNA degradation and/ortranslational repression. Through down-regulating the expression of targetgenes, miRNAs play pivotal roles in a number of physiological andpathological processes, such as cell differentiation, proliferation,apoptosis, migration and carcinogenesis . Accumulating studies haveindicated that aberrant expression of specific miRNAs is implicated in HCCdevelopment and progression [6, 7]. For example, miR-122, a liver-specificmiRNA, is frequently down-regulated in HCC  and inhibits tumor growth bydown-regulating cyclin G1 . MiR-139-5p (denoted thereafter as miR-139) isanother miRNA that plays important roles in HCC. It is located within thesecond intron of the phosphodiesterase 2A (PDE2A) gene on chromosome 11q13.4  and is often under-expressed in HCC. MiR-139mainly functions as a tumor suppressor in HCC; it can suppress theproliferation, migration and invasion of HCC cells and induce HCC cellapoptosis via down-regulating a number of target genes, such as T-cell factor-4 (TCF-4) , Rho-kinase 2 (ROCK2) , zinc finger E-box binding homeobox 1(ZEB1) and ZEB2 . Notably, the number of studies of miR-139 in HCC is still very limitedand the function(s) of miR-139 in HCC development remains largely unknown.Therefore, further investigation in the role of miR-139 in HCC is ofessential significance.
We also investigated the effects of miR-139 overexpression on the migrationand invasion abilities of Hep3B and SMMC7721 cells. The transwell migrationassay indicated that overexpression of miR-139 significantly suppressedmigration of both cell lines (Fig. 3a and b). Furthermore, the invasion assayshowed that ectopic expression of miR-139 also resulted in significantlyattenuated invasion ability of Hep3B and SMMC7721 cells (Fig. 3c and d).Epithelial-to-mesenchymal transition (EMT) has been shown to play importantroles in regulating cell migration and invasion. Therefore, we furtherinvestigated the influence of deregulated miR-139 expression in theexpression of EMT markers. The results revealed that in cells overexpressingmiR-139, the protein level of E-cadherin, an epithelial marker, wasup-regulated, while expression of Vimentin, a mesenchymal marker, wassuppressed (Fig. 3e). In addition, the level of an important inducer of EMT,snail family transcriptional repressor 1 (SNAIL1), was not affected (Fig.3e). On the contrary, in the cells with down-regulated expression of miR-139,E-cadherin level was down-regulated, while Vimentin expression wasup-regulated, and SNAIL1 expression remained unchanged (Fig. 3f). Theseresults indicated that miR-139 might inhibit HCC cell migration and invasionvia regulating the epithelial-mesenchymal plasticity.
KPNA2 mRNA transcript exhibits a putative target sequence for miR-139 in 3'UTR and is predicted as a direct target of miR-139 by miRanda (Fig. 5a). Inaddition, several studies based on high-throughput sequencing also identifiedKPNA2 as a candidate target of miR-139 [24-26]. However, no study hasestablished their direct regulatory relationship. Firstly, we analyzed theLIHC dataset for the correlation between miR-139 and KPNA2 level. We foundthat KPNA2 mRNA level in HCC tissues was significantly higher than that ofnon-cancerous tissues (Fig. 5b). In addition, KPNA2 mRNA level was increasedin HCC patients at more advanced pathological stages (Fig. 5c). We alsoidentified a negative correlation between miR-139 and KPNA2 levels (r = - 0.4551, p < 0.0001, Fig. 5d). We then determined the effects of miR-139overexpression on the endogenous mRNA and proteins levels of KPNA2 in Hep3Band SMMC7721 cells. The results indicated that the mRNA (Fig. 5e) and protein(Fig. 5f) levels of KPNA2 were both significantly down-regulated in cellsover-expressing miR-139 compared to control cells. To determine whether KPNA2was a direct target of miR-139 in HCC, we constructed luciferase reporterplasmids containing parts of KPNA2 3'UTR with either a wildtype ordeleted miR-139 target sites and performed the luciferase reporter assay inHep3B cells. As shown in Fig. 5g, transfection of miR-139 mimics suppressedthe Renilla luciferase activity of the reporters containing wild-type miR-139targeting site of KPNA2, while the Renilla luciferase activity of thereporter plasmid containing deleted miR-139 target sites was notsignificantly reduced. On the contrary, transfection of anti-miR-139 oligoscaused elevated Renilla luciferase activity of wild type luciferase reporter,but the Renilla luciferase activity of mutant reporter remained unchanged(Fig. 5h). These results confirmed that KPNA2 mRNA transcript was directlytargeted by miR-139 in HCC cells.
KPNA2 is a direct target of miR-139. a A schematic illustration of the targeting sites of miR-139 in the 3'UTR of KPNA2 mRNA transcript and the luciferase reporter plasmids containing parts ofKPNA2 3'UTR with either a wildtype or deleted miR-139 target sites. b-d KPNA2 mRNA level was retrieved from the LIHC dataset in TCGA. b KPNA2 level was compared between HCC tissues and non-cancerous tissues. c KPNA2 level in HCC patients at different pathological stages. d The correlation analysis for the association between miR-139 and KPNA2levels. e and (f) Hep3B and SMMC7721 cells were transfected with miR-139 mimics or controloligos. The (e) mRNA and (f) proteins levels of KPNA2 were analyzed by qRT-PCR and western blot,respectively. g In Hep3B cells the luciferase reporter assay was performed. MiR-139 mimicsand the reporter plasmids or control vectors were co-transfected into thecells. The Renilla and firefly luciferase activities of the reporters orvectors were measured with the Dual-Glo assay. h The anti-miR-139 oligos and the reporter plasmids or control vectors wereco-transfected into the Hep3B cells. The Renilla and firefly luciferaseactivities of the reporters or vectors were measured with the Dual-Glo assay.All experiments were repeated 3 times. * P < 0.05, ** P < 0.01, *** P < 0.001
MiR-139 expression is frequently suppressed in HCC [12, 27, 28, 31]. In thisstudy, we also found that miR-139 was down-regulated in HCC cell lines andtissues. The reason for the down-regulation of miR-139 in cancers has beenrarely studied. Epigenetic regulation has been reported to silence theexpression of miR-139 at transcriptional level. Bao et al. found that CD44binds directly to HER2 to induce deacetylation of histone H3 lysine 9 andsuppresses transcription of miR-139 in gastric cancer cells . Watanabe etal. has shown that miR-139 was epigenetically silenced by histone H3 lysine27 trimethylation (H3K27me3) of its host gene PDE2A in NSCLC .Furthermore, miR-139 level also can be regulated post-transcriptionally. Forexample, long non-coding RNA XIST  and LINC00152  can down-regulatethe expression of miR-139 via acting as "sponges" in bladder cancerand CRC, respectively. However, the mechanism for regulating miR-139 level inHCC has not been reported yet. We treated the HCC cells with 5-AZA, a DNAmethyltransferase inhibitor or TSA, a histone deacetylase inhibitor. Only theTSA treatment restored the expression of miR-139 in HCC, suggesting increasedhistone acetylation might contribute to the down-regulation of miR-139expression in HCC. Several studies have indicated the significance of miR-139down-regulation in HCC. Wong et al. showed that down-regulation of miR-139 inHCC was associated with advanced tumor stages and poor prognosis . TheLIHC dataset in the TCGA contains a much larger cohort of HCC patients andcomprehensive characterization of each sample. To further confirm thesignificance of under-expression of miR-139 in HCC, we analyzed thecorrelation between miR-139 level and clinicopathological features HCCpatients based on the LIHC cohort. We also found that low miR-139 level wasassociated with advanced stage of the disease and dismal patient survival(Fig. 1), in consistence with the reported studies. These data stronglysuggested that miR-139 plays a tumor suppressive role in HCC. 2b1af7f3a8