"Gene amplification causes overexpression" is a longstanding and well-accepted concept in cancer genetics. However, raking the whole literature, we find only statistical analyses showing a positive correlation between gene copy number and expression level, but do not find convincing experimental corroboration for this notion, for most of the amplified oncogenes in cancers. Since an association does not need to be an actual causal relation, in our opinion, this widespread notion still remains a reasonable but unproven assumption awaiting experimental verification.

Recent genomic and ribonomic research reveals that our genome produces a stupendous amount of non-coding RNAs (ncRNAs), including antisense RNAs, and that many genes contain other gene(s) in their introns. Since ncRNAs either regulate the transcription, translation or stability of mRNAs or directly exert cellular functions, they should be regarded as the fourth category of RNAs, after ribosomal, messenger and transfer RNAs. These and other research advances challenge the current concept of gene and raise a question as to how we should redefine gene. We can either consider each tiny part of the classically-defined gene, such as each mRNA variant, as a “gene”, or, alternatively and oppositely, regard a whole genomic locus as a “gene” that may contain intron-embedded genes and produce different types of RNAs and proteins. Each of the two ways to redefine gene not only has its strengths and weaknesses but also has its particular concern on the methodology for the determination of the gene's function: Ectopic expression of complementary DNA (cDNA) in cells has in the past decades provided us with great deal of detail about the functions of individual mRNA variants, and will make the data less conflicting with each other if just a small part of a classically-defined gene is considered as a “gene”. On the other hand, genomic DNA (gDNA) will better help us in understanding the collective function of a genomic locus. In our opinion, we need to be more cautious in the use of cDNA and in the explanation of data resulting from cDNA, and, instead, should make delivery of gDNA into cells routine in determination of genes' functions, although this demands some technology renovation.

Background: Dynamic SUMO modifications play crucial roles in orchestrating cellular response to various stimuli, including viral infection, and hold significant therapeutic potential. The Spike (S) protein, a surface glycoprotein of SARS-CoV-2 (a global health threat), serves as the key mediator for viral entry and is a critical target for drug development. However, the function of SUMOylation in the Spike protein remains largely unclear.