{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:09:19Z","timestamp":1781114959048,"version":"3.54.1"},"reference-count":30,"publisher":"Scientific Scholar","content-domain":{"domain":["ijmr.org.in"],"crossmark-restriction":true},"short-container-title":["Indian J Med Res"],"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Hypoxia is the critical hallmark of solid tumours, including oral squamous cell carcinoma (OSCC),\u00a0which\u00a0is the most prevalent cancer in the Indian subcontinent. Sphingosine kinase 1 (SphK1) is a known oncogene that is upregulated in most cancers, including OSCC. However, its regulation in the development and progression of OSCC is unknown. The objective of the study was to determine the regulation of SphK1\n                      <jats:italic>via<\/jats:italic>\n                      hypoxia-inducible factors (HIFs) in OSCC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Tumour and adjacent normal tissues from 70 OSCC patients were collected and snap frozen. Quantitative real-time PCR (qRT-PCR) measured\n                      <jats:italic>SPHK1, HIF1A, HIF2A<\/jats:italic>\n                      expression, and the downstream target of HIF-1\u03b1 expression. Spearman correlation analysis assessed the association between\n                      <jats:italic>SPHK1<\/jats:italic>\n                      and\n                      <jats:italic>HIF1A\/HIF2A<\/jats:italic>\n                      . Tongue squamous cancer cells, SCC-9 and SCC-25, were treated with CoCl\n                      <jats:sub>2<\/jats:sub>\n                      or 1% oxygen to induce hypoxia, with or without KC72F (a HIF-1\u03b1 inhibitor). The SPHK1 promoter was cloned into a pGL3 vector, and luciferase reporter assays were performed in SCC-9 and SCC-25 cells. Stable SphK1 knockdown cells were generated using shRNA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HIF1A was overexpressed in 73% of oral squamous cell carcinoma (OSCC) tumours, strongly correlating with\n                      <jats:italic>SPHK1<\/jats:italic>\n                      expression. Stabilising HIF-1\u03b1 through CoCl\u2082 or hypoxia-induced SPHK1 expression was reversed by the HIF-1 inhibitor. The knockdown of\n                      <jats:italic>SPHK1<\/jats:italic>\n                      in OSCC cells reduced the stability of HIF-2\u03b1, but not HIF-1\u03b1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation and conclusion<\/jats:title>\n                    <jats:p>\n                      Our study revealed that\n                      <jats:italic>SPHK1<\/jats:italic>\n                      expression is upregulated through HIF-1\u03b1, which in turn stabilises HIF-2\u03b1. Thus, inhibition of SphK1 along with HIF-2\u03b1 might be beneficial for the management of OSCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.25259\/ijmr_3381_2025","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:43:43Z","timestamp":1781113423000},"page":"701-709","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sphingosine kinase 1 is dysregulated\n                    <i>via<\/i>\n                    hypoxia-inducible factor 1\u03b1 in oral squamous cell carcinoma"],"prefix":"10.25259","volume":"163","author":[{"given":"Ritu","family":"Pandey","sequence":"first","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Vishwakarma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saikat","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"10.25259\/IJMR_3381_2025\/ref-1","doi-asserted-by":"publisher","first-page":"100046","DOI":"10.1016\/j.sintl.2020.100046","article-title":"Oral cancer diagnosis and perspectives in India","volume":"1","author":"Borse","year":"2020","journal-title":"Sens Int."},{"key":"10.25259\/IJMR_3381_2025\/ref-2","doi-asserted-by":"publisher","first-page":"1505833","DOI":"10.3389\/froh.2024.1505833","article-title":"Current trends on prevalence, risk factors and prevention of oral cancer","volume":"5","author":"Coletta","year":"2024","journal-title":"Front Oral Health."},{"key":"10.25259\/IJMR_3381_2025\/ref-3","doi-asserted-by":"publisher","first-page":"3721","DOI":"10.3390\/curroncol30040283","article-title":"Oral Squamous cell carcinoma and concomitant primary tumors, what do we know? 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