SPRY4 and gastric cancer: UBR2 activates the Erk/MAPK pathway by inhibiting the negative regulator of the pathway through ubiquitination.148 Lymphatic metastasis, a standard route of metastasis in GC, is caused by the miR-877-3p/VEGFA and SPRY4-IT1/miR-101-3p/AMPK axes mediated by overexpression of circRanGAP1 and lncRNA SPRY4-IT1, respectively.149,150 These molecules, circRanGAP1, and SPRY4-IT1, are closely associated with the progression, lymphatic metastasis, and poor survival in GC.