PMID- 36553522
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230109
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 13
IP  - 12
DP  - 2022 Nov 30
TI  - Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role in 
      Hepatocellular Carcinoma from an in Silico Perspective.
LID - 10.3390/genes13122254 [doi]
LID - 2254
AB  - Hepatocellular carcinoma (HCC) is a complex disease involving altered 
      interactomes of transcripts and proteins. MicroRNAs (miRNAs) are small-noncoding 
      RNAs that can interact with specific gene transcripts and an array of other vital 
      endogenous non-coding RNAs (lncRNAs) that can influence gene expression. 
      Maternally Expressed Gene 3 (MEG3) is an imprinted lncRNA that is reported to be 
      downregulated in HCC (in both cell lines and tumors). Alcohol Dehydrogenase 4 
      (ADH4) is a well-known prognostic protein biomarker for predicting the survival 
      outcomes of patients with hepatocellular carcinoma whose expression is regulated 
      by miR-664a-3p, which is upregulated in HCC. In this study, we performed a 
      battery of robust and systematic in silico analyses to predicate the possible 
      lncRNA-miRNA interactions between MEG3, miR-664a-3p, and ADH4. miRNA-mRNA and 
      lncRNA-miRNA hybrid structures were primarily obtained, and the minimum free 
      energies (MFEs) for the 3'UTR (Untranslated Regions) of ADH4-miR-664a-3p and the 
      3'UTR of MEG3-miR-664a-3p interactions were assessed to predict the stability of 
      the obtained RNA heteroduplex hybrids. The hybrid with the least minimum free 
      energy (MFE) was considered to be the most favorable. The MFEs were around -28.1 
      kcal/mol and -31.3 kCal/mol for the ADH4-miR-664a-3p and MEG3-miR-66a-3p RNA 
      hybrids, respectively. This demonstrated that lncRNA-MEG3 might be a competitive 
      endogenous RNA that acts as a molecular sponge for miR-664a-3p. In summary, our 
      interaction analyses results predict the significance of the 
      MEG3/miR-664a-3p/ADH4 axis, where MEG3 downregulation results in miR-664a-3p 
      overexpression and the subsequential underexpression of ADH4 in HCC, as a novel 
      axis of interest that demands further validation.
FAU - Karunakara, Shreyas H
AU  - Karunakara SH
AD  - Department of Biochemistry, Center of Excellence in Molecular Biology & 
      Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and 
      Research, Mysore 570015, India.
FAU - Puttahanumantharayappa, Lakshana D
AU  - Puttahanumantharayappa LD
AD  - Department of Biochemistry, Center of Excellence in Molecular Biology & 
      Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and 
      Research, Mysore 570015, India.
FAU - Sannappa Gowda, Nirmala G
AU  - Sannappa Gowda NG
AD  - Department of Biochemistry, Center of Excellence in Molecular Biology & 
      Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and 
      Research, Mysore 570015, India.
FAU - Shiragannavar, Varsha D
AU  - Shiragannavar VD
AD  - Department of Biochemistry, Center of Excellence in Molecular Biology & 
      Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and 
      Research, Mysore 570015, India.
FAU - Santhekadur, Prasanna K
AU  - Santhekadur PK
AUID- ORCID: 0000-0003-3338-375X
AD  - Department of Biochemistry, Center of Excellence in Molecular Biology & 
      Regenerative Medicine, JSS Medical College, JSS Academy of Higher Education and 
      Research, Mysore 570015, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221130
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (3' Untranslated Regions)
RN  - EC 1.1.1.1 (alcohol dehydrogenase IV)
RN  - 0 (MicroRNAs)
RN  - 0 (Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (MEG3 non-coding RNA, human)
RN  - 0 (MIRN664 microRNA, human)
SB  - IM
MH  - Humans
MH  - 3' Untranslated Regions
MH  - *Carcinoma, Hepatocellular/pathology
MH  - *Liver Neoplasms/pathology
MH  - *MicroRNAs/metabolism
MH  - Proteins/genetics
MH  - *RNA, Long Noncoding/metabolism
PMC - PMC9778073
OTO - NOTNLM
OT  - MEG3
OT  - alcohol dehydrogenase 4
OT  - hepatocellular carcinoma
OT  - mean binding energy
OT  - miR-664a-3p
OT  - tumor suppressor
COIS- The authors declare no conflict of interest.
EDAT- 2022/12/24 06:00
MHDA- 2022/12/27 06:00
PMCR- 2022/11/30
CRDT- 2022/12/23 01:22
PHST- 2022/10/21 00:00 [received]
PHST- 2022/11/19 00:00 [revised]
PHST- 2022/11/28 00:00 [accepted]
PHST- 2022/12/23 01:22 [entrez]
PHST- 2022/12/24 06:00 [pubmed]
PHST- 2022/12/27 06:00 [medline]
PHST- 2022/11/30 00:00 [pmc-release]
AID - genes13122254 [pii]
AID - genes-13-02254 [pii]
AID - 10.3390/genes13122254 [doi]
PST - epublish
SO  - Genes (Basel). 2022 Nov 30;13(12):2254. doi: 10.3390/genes13122254.