The problem is one of picking out pieces. A "normal" s/// won't work, but a cheeky (?{code block}) does:

#!/your/perl/here

use strict;
use warnings;

my $one   = q/in ('X')/;
my $two   = q/in ('X','Y')/;
my $three = q/in ('X','Y','Z')/;

foreach my $s ( $one, $two, $three )
{
    our $r='';
    (my $u = $s) =~ s{            # open regex - curly delimiters
                      in\s+
                       \(         # literal open paren
                       (?:        # non-capturing group
                          '       # literal single quote
                           (      # capture group
                            [^']  # single non-single-quote-char
                           )      # close capture group
                           (?{$r=$r.$^N})
                          '       # literal single quote
                       )          # closing non-capture group
                       (?:        # opening non-capture group
                          ,'      # literals
                            (     # capture group
                             [^'] # single non-single-quote-char
                            )     # close capture group
                            (?{$r=$r.$^N})
                           '      # literal single-quote
                        )*        # close non-capture group
                       \)         # literal close paren
                     }            # close regex - curly delimiter
                     {=~\ m/\[$r\]}x;
    print "$s\n$u\n\n";
}
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But that's not usually a good idea.