If we are in a simulation, then there is a possibility that our creators are in a simulation as well. But no matter how far up the chain you go, eventually someone has to be real. So even if we are in a simulation, the information that represents us is still very real, in the sense that it is being stored within a real universe.
The fact that we are sentient and capable of experiencing, rather than simply being an organic automaton, suggests that there is more to the universe than what physics can currently explain. We don’t really know what sentience is or if it even exists, but the answer might shed light on whether we are in a simulation.
Imagine you made a giant Conway’s Game of Life and it ended up evolving into a society like ours. The people in the simulation have thoughts and emotions not unlike your own. You aren’t sure if they are sentient, but you can’t be sure about anyone else in the real world anyway. You might as well consider the stimulated people to be as real as you are.