P38 inhibited cutaneous squamous cell carcinoma associated long intergenic non-protein coding RNA (PICSAR)

PICSAR (P38 inhibited cutaneous squamous cell carcinoma associated long intergenic non-protein coding RNA, also known as LINC00162 and other aliases), is a long intergenic non-coding RNA first identified as highly upregulated in cutaneous squamous cell carcinoma (cSCC) compared to normal skin. PICSAR is specifically expressed by tumor cells, but absent from normal keratinocytes. Its expression is upregulated when p38 MAPK is inhibited; mechanistically, PICSAR promotes tumor growth and metastasis by suppressing DUSP6—a negative regulator of ERK1/2—and thereby activating MAPK/ERK signaling. PICSAR acts as a competing endogenous RNA, sequestering miR-485–5p and derepressing specific cancer-associated genes such as PAQR4. Knockdown of PICSAR inhibits tumor cell proliferation, migration, and chemoresistance in vitro and in xenograft models. Beyond oncology, PICSAR expression may also serve as a non-invasive biomarker for rheumatoid arthritis, correlating with severity scores and disease progression. Despite promising preclinical data, PICSAR-targeted drugs are not yet available, and safety/efficacy remain to be established in clinical trials.

Other names

LINC00162Lnc-NLC1-CNarcolepsy candidate region 1 gene CC21orf113NCRNA00162NLC1-CNLC1CPRED74Putative narcolepsy candidate region 1 gene C proteinLong intergenic non-protein coding RNA 162

Inhibition of p38 MAPK upregulates PICSAR (targeting p38 MAPK will decrease PICSAR expression). PICSAR knockdown suppresses cancer cell proliferation and migration and inhibits tumor growth in vivo by restoring negative regulation of ERK1/2 via DUSP6. PICSAR functions as a molecular sponge, sequestrating miR-485–5p and deregulating target genes such as PAQR4.